Dopaminergic Neurotransmision Research Papers - Academia.edu (original) (raw)

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- Decision Making, Addiction, Discrete Choice Modeling, Dopaminergic Neurotransmision

Multiple theories of Attention-Deficit/Hyper-activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.

- by Marcel Kinsbourne and +2
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- Attention-Deficit/Hyperactivity Disorder, ADHD (Psychology), Attention, Dopaminergic Neurotransmision

This study offers a unique approach to consumer/tourist behaviour called psychoneurobiochemistry and aims to explore the possible and potential influences of psychoneurobiochemical factors on tourism marketing. The study with a... more

- by Hakan BOZ
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- Marketing, Biochemistry, Neuroscience, Psychology

An influential theory within personality neuroscience suggests that trait extraversion is underpinned by individual differences in dopamine function. In a review of the relevant literature, we evaluate this theory in light of the evidence from molecular genetics, neuroimaging, and psychopharmacology. Evidence linking individual differences in extraversion with dopamine-relevant genes, structural volume of dopamine-rich brain regions (e.g., in striatal and ventral prefrontal areas), dopamine receptor availability, and frontal alpha asymmetry is mixed at best. Evidence concerning both scalp recorded (electroencephalogram) and hemodynamic (functional magnetic resonance imaging) neural responses to rewards appears somewhat more promising. Perhaps the best evidence concerns extraversion- dependent responses – both neural and behavioural – to dopaminergic drugs. Future research in this area must go beyond the demonstration of theoretically consistent associations and attempt to provide more specific causal evidence for the dopamine hypothesis of extraversion. A further challenge is to expand this hypothesis to incorporate other neurobiological processes that are likely to underlie this trait.

- by Luke Smillie
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- Personality Psychology, Personality, Dopaminergic Neurotransmision, Dopamine
- by Dimitris Xygalatas
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- Religion, History, Evolutionary Biology, Neuroscience

Recent advances in the study of alcoholism have thrown
light on the involvement of various neurotransmitters in the
phenomenon of alcohol addiction. Various neurotransmitters
have been implicated in alcohol addiction due to their
imbalance in the brain, which could be either due to their
excess activity or inhibition. This review paper aims to
consolidate and to summarize some of the recent papers
which have been published in this regard. The review
paper will give an overview of the neurobiology of alcohol
addiction, followed by detailed reviews of some of the recent
papers published in the context of the genetics of alcohol
addiction. Furthermore, the author hopes that the present
text will be found useful to novices and experts alike in the
field of neurotransmitters in alcoholism.

Despite similar emotional deficiencies, primary psychopathic individuals can be situated on a continuum that spans from controlled to disinhibited. The constructs on which primary psychopaths are found to diverge, such as self-control, cognitive flexibility, and executive functioning, are crucially regulated by dopamine (DA). As such, the goal of this review is to examine which specific alterations in the meso-cortico-limbic DA system and corresponding genes (e.g., TH, DAT, COMT, DRD2, DRD4) might bias development towards a more controlled or disinhibited expression of primary psychopathy. Based on empirical data, it is argued that primary psychopathy is generally related to a higher tonic and population activity of striatal DA neurons and lower levels of D2-type DA receptors in meso-cortico-limbic projections, which may boost motivational drive towards incentive-laden goals, dampen punishment sensitivity, and increase future reward-expectancy. However, increasingly higher levels of DA activity in the striatum (moderate versus pathological elevations), lower levels of DA functionality in the prefrontal cortex, and higher D1-to-D2-type receptor ratios in meso-cortico-limbic projections may lead to increasingly disinhibited and impetuous phenotypes of primary psychopathy. Finally, in order to provide a more coherent view on etiological mechanisms, we discuss interactions between DA and serotonin that are relevant for primary psychopathy.

- by Baris O. Yildirim and +1
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- Aggression (Psychology), Personality Disorders, Psychopathology, Dopaminergic Neurotransmision

The doping starts since we wake up drinking a coffee or when we can´t sleep and we take a sleeping pill; there´s so many kinds to doping up if we considerate the definition that says: doping it’s be dependent to a substance. But we have... more

- by Nery Martinez
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- Football (soccer), Dopaminergic Neurotransmision, Sport, Futbol

Recent research suggests that romantic love may be literally addictive. Although the exact nature of the relationship between love and addiction has been described in inconsistent terms throughout the literature, we offer a framework that distinguishes between a narrow view and a broad view of love addiction. The narrow view counts only the most extreme, harmful forms of love or love-related behaviors as being potentially addictive in nature. The broad view, by contrast, counts even basic social attachment as being on a spectrum of addictive motivations, underwritten by similar neurochemical processes as more conventional addictions. We argue that on either understanding of love-as-addiction, treatment decisions should hinge on considerations of harm and well-being rather than on definitions of disease. Implications for the ethical use of anti-love biotechnology are considered.

- by Brian D . Earp
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- Business Ethics, History, Cultural History, Pharmacology

Neurochemistry and drug addiction. Neurocognitive approach. Cognitive Neuroscience. Research for the Postgraduate Program in Cognitive Sciences of the University of Costa Rica. This research establishes a theoretical basis for the biochemical and neurophysiological bases of behavior and mental phenomena, as well as analyzing the neuropathologies derived from the consumption of toxic substances. Plausible explanations are given for the relationships between toxic and addictive and addictive behaviors, and their neurophysiological and genetic bases. // Neuroquímica y toxicodependencia. Enfoque de neurocognoscitivo. Neurociencias Cognoscitivas. Investigación para el Programa de Postgrado en Ciencias Cognoscitivas de la Universidad de Costa Rica. Esta investigación, establece una fundamenta teórica de las bases bioquímicas y neurofisiológicas de la conducta y de los fenómenos mentales, así como analiza las neuropatologías derivadas del consumo de tóxicos. Se plantean explicaciones plausibles de las relaciones entre tóxicos y conductas dependientes y adictivas, y sus bases neurofisiológicas y genéticas. // Rodolfo J. Rodríguez-Rodríguez. E-Mail: rodolfojrr@gmx.com

RESUMEN
El presente artículo se propone dar cuenta del elusivo fenómeno de la conciencia desde la original perspectiva de la neurofenomenología de Francisco Varela, quien a partir de nociones tales como neuroplasticidad, enacción y emergencia, explica, cómo ocurren los procesos cerebrales que fundan la conciencia y la “unidad” de la vivencia. Describiendo como la conciencia aparece en el vivir encarnado: en la regulación con el cuerpo entero; en sus relaciones sensorio-motoras con el mundo y en una red ínter-subjetiva de acciones y de lenguaje.
Dr. Adolfo Vásquez Rocca
Keywords: Neurociencias, ciencias cognitivas, ética, yo, cuerpo, neuroplasticidad, enacción, acciones corporeizadas, biología cultural, saber-cómo.
Neuroscience, cognitive science, ethics, self, body, neuroplasticity, enaction, actions embodied experiences, cultural biology, know-how.
-Francisco Varela: neurophenomenology, enactive approach to cognition, minds without me and the elusive phenomenon of consciousness.
DR. ADOLFO VÁSQUEZ ROCCA

- by Adolfo Vasquez Rocca
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- Critical Theory, Neuroscience, Sociology, Cultural Studies

Introduction: Genetic variants within nicotinic receptors have been shown to modulate an individual’s risk for nicotine dependence. Among the most reproducible risk factor is a non-synonymous polymorphism (rs16969968) within the alpha5 nicotinic receptor subunit gene, CHRNA5. Genetic factors also contribute to CHRNA5 mRNA expression and risk for substance abuse, but the specific variants responsible for changes in mRNA expression are unclear. Methodology: To determine the presence of cis-acting functional genetic variants contributing to CHRNA5 mRNA expression, we measured allelic expression of CHRNA5 within post-mortem human prefrontal cortex brain tissue. Using allelic expression as a phenotype, we scanned the CHRNA5 gene locus for polymorphisms responsible for imbalanced allelic expression. Polymorphisms determined to be responsible for allelic expression were genotyped in our full brain cohort and total CHRNA5 expression was compared across genotype using quantitative PCR. We then tested these expression-related variants for clinical association with nicotine dependence. Results: We uncovered a functional genetic locus 13.5kb upstream of CHRNA5 acting as an enhancer of CHRNA5 mRNA expression. Minor allele carriers for enhancer variants displayed >2- fold differences in allelic expression, while individuals homozygous for the enhancer minor alleles expressed >4-fold more cortical CHRNA5 mRNA. Haplotype structure analysis predicts that the enhancer SNPs rarely occur on the same allele as the previously implicated non-synonymous variant. Taking into account this relationship, enhancer region SNPs confer significant risk only when you control for the presence of the non-synonymous variant in a joint SNP analysis. Conclusions: Polymorphisms within a transcriptional enhancer located 13.5kb upstream of CHRNA5 modulate CHRNA5 mRNA transcription. These enhancer variants confer risk for nicotine dependence in a context-dependent manner. Understanding the biological functions of these clinically relevant genetic variants revealed a SNP-SNP interaction increasing risk for nicotine dependence that is otherwise obscured by haplotype structure when using traditional clinical association methods. These findings aid in the construction of complex biological or genetic models of nicotine dependence that mimic human factors. The relevance of the enhancer CHRNA5 polymorphism in other brain regions and peripheral tissues (e.g., the lung) needs further study. Moreover, identification of functional CHRNA5 variants facilitates the analysis of gene-gene interactions with respect to nicotine and other drug addictions.

This paper reviews two of the major features of the nigrostriatal pathway, its axonal collateralization, and compartmental specificity, as revealed by single-axon labeling experiments in rodents and immunocytological analysis of human postmortem tissue. The dorsal and ventral tiers of the substantia nigra pars compacta harbor various types of neurons the axons of which branch not only within the striatum but also in other major components of the basal ganglia. Furthermore, some nigrostriatal axons send collaterals both to thalamus and to brainstem pedunculopontine tegmental nucleus. In humans, the compartmental specificity of the nigrostriatal pathway is revealed by the fact that the matrix compartment is densely innervated by dopaminergic fibers, whereas the striosomes display different densities of dopaminergic terminals depending on their location within the striatum. The nigral neurons most severely affected in Parkinson's disease are the ventral tier cells that project to the matrix and form deep clusters in the substantia nigra pars reticulata.

- by Javier Bernácer
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- Dopaminergic Neurotransmision, Learning, Motivation, Dopamine

The Sanctuary of Dionysos Eleuthereus on the southeast slope of the Acropolis in Athens and the theatron that was erected above it was the major and performance venue for fifth century Athenian drama. It is quite possible that almost every play from that period was created specifically for this space. 1 I suggest that we can learn a great deal more about the original reception of the plays in performance by applying research from the affective sciences to the evidence of material culture and the texts of the plays themselves. Here I focus on the relationship of the spectator to the environment within which the theatre was located -in particular the stunning view of the landscape, sea and sky. I apply the four spatial realms theory of Previc to the theatre space and following Previc's research, suggest that the relationship of the performance space to its view created a deep spiritual experience that cannot be recreated on the modern interior stage. There was a reason why Plato, Aristotle and Isocrates all described the theatre as possessing the power -to move the soul‖: this paper is part of a larger study that is seeking to better understand how ancient Greek drama achieved this. This is an exciting time for those of interested in the theatre of ancient Greece, recent studies have begun again to probe the important questions of origins and influences, epigraphic evidence is shining new light on the organization and financing of the theatre and new ongoing archaeological surveys of the site of the Theatre of Dionysos in Athens are starting to reveal some fascinating new information. My current book length project is to combine this new material with a cognitive approach to the theatre. I am interested in the reception of ancient drama, but in this case, the reception of the original audience, and while we can never hope to fully

- by Peter Meineck
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- Cognitive Psychology, Greek Tragedy, Theatre Studies, Theatre History

Parkinson’s disease is a progressive neurodegenerative disorder of the basal ganglia for which no specific cause could be found in the majority of cases. For a long time a possible role for an environmental toxin (s) in a genetic background has been thought. Pesticides and insecticides were implicated in the increased prevalence of PD in rural areas. Rotenone is a plant derived pesticide and a complex I (NADH-quinone oxido-reductase) inhibitor. In rodents, the pesticide administered via systemic routes as well as locally into specific brain areas eg., the substantia nigra or striatum, resulted in nigrostraital cell loss, α-synuclein like cytoplasmic inclusions, and motor impairments. Rotenone induces decreased dopamine and tyrosine hydroxylase immunoreactive neurons in the striatum and substantia nigra. Changes in serotonergic, noradrenergic, and cholinergic neurotransmitters also occur. Parkinsonian like α-synuclein pathology also develops inside the spinal cord, dorsal motor nucleus of the vagus as well as in the enteric neurons in rotenone-treated rodents. Oxidative and nitrosative stress, mitochondrial dysfunction, dysfunction of the ubiquitin-proteasome pathway, protein aggregation, microtubule depolymerization, excitotoxicity, microglia activation, and neuroinflammation have been identified as important mechanisms underlying the rotenone-induced death of dopaminergic neurons. Research into the rotenone model of PD offers many possibilities for studying the pathways of cell death in PD and developing new drug therapies.

- by Jacobs Publishers
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- Parkinson's Disease, Dopaminergic Neurotransmision, Pesticides, Cell Death

There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.

- by Nora S Vyas
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- Genetics, Neuroscience, Psychosis, Child and adolescent mental health

BACKGROUND: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). A dopamine-responsive abnormality of brain function in TS could be either presynaptic or postsynaptic. Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release. Alternatively, presynaptic dopaminergic function could be normal in TS but dopamine-sensitive abnormalities could exist in striatum, pallidum, thalamus, or cortex. METHODS: In this study we directly tested the presynaptic hypothesis using a new approach. We used positron emission tomography (PET) and [11C]raclopride (RAC*) to measure synaptic dopamine release in response to levodopa and placebo infusions (with carbidopa) in 5 neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain. RESULTS: (1) Overall, baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND was higher in TS (16%, p=0.051). (2) Across regions, DA release declined from before to during infusion (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BPND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects, and in parahippocampal gyrus (p=0.02, corrected). DISCUSSION: Our finding that a before/after RAC* design is confounded by time and/or expectation effects has implications for other RAC* PET studies. The smaller magnitude of the decrease with time in TS may be attributable to impaired habituation to the scan environment. Levodopa’s opposite effect on RAC* binding in TS dopaminergic midbrain was not predicted, but may signify an abnormal response to dopaminergic stimulation in TS. These findings invite confirmation in a larger sample.

Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of " synapse-based " psychiatric therapeutic strategies.

- by Domenico De Berardis and +3
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- Psychopharmacology, Neuropharmacology, Dopaminergic Neurotransmision, Molecular Psychiatry

In the philosophical literature, self-deception is mainly approached through the analysis of paradoxes. Yet, it is agreed that self-deception is motivated by protection from distress. In this paper, we argue, with the help of findings from cognitive neuroscience and psychology, that self-deception is a type of affective coping. First, we criticize the main solutions to the paradoxes of self-deception. We then present a new approach to self-deception. Self-deception, we argue, involves three appraisals of the distressing evidence: (a) appraisal of the strength of evidence as uncertain, (b) low coping potential and (c) negative anticipation along the lines of Damasio's somatic marker hypothesis. At the same time, desire impacts the treatment of flattering evidence via dopa-mine. Our main proposal is that self-deception involves emotional mechanisms provoking a preference for immediate reward despite possible long-term negative repercussions. In the last part, we use this emotional model to revisit the philosophical paradoxes.

- by Federico Lauria
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- Cognitive Psychology, Cognitive Science, Psychoanalysis, Emotion
- by Nora S Vyas
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- Neuroscience, Psychology, Cognitive Science, Psychiatry

Psychological neural circuits are comprised of Dopaminic and Norepic work stations, that can be compared to logic gates; while the Norepic workstation can be called the biological “And” Gate, the Dopaminergic work station can be called a simple “booster gate”, for which no standard comparisons exist. These are the two elegantly-designed biological gates which control much of our "quantum psychological" (infinitesimal boosts in signalling) operations. The most important finding is the cause of Alzheimer’s disease. If more Dopaminergic work stations are present in a given individual; if his neurostructural ideology is more Dopaminergic/Dopaminic (in parallel, he will suffer a Norepinephrine deficiency, which is better known as "Dopamine beta hydroxylase deficiency" – such a neurostructural ideology translates, as shown in this paper, into a higher electric signal density, i.e., overly strong (cumulatively) flows of current in certain neural regions, which leads to neuronal collapses due to unidentified reasons that may be any of the following (or their combinations): chemical stress, mechanical stress (e.g.: fatigue), and/or overheating. This, then, is the cause of dementia. Neuronal collapses brought about by dangerous current surges is nothing but dementia. Neuroinflammation, often wrongly regarded as the culprit behind AD, seems to be merely a repair reaction. The pathogenic detail is not just that there is too less Norepi in the brain – "The loss of noradrenergic [Norepic] neurons is a striking feature of dementia (AD)" – but also that there is too much Dopaminergic logic gate control, in particular identifiable types of brains whose owners may contract dementia if the gross mental metabolic rate is not controlled.

- by Anand M Kumar
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- Evolutionary Biology, Neuroscience, Psychology, Cognitive Psychology

, especially the Cav1.3-subtype, generate an activity-related oscillatory Ca 2+ burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PDtherapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtypelike, sensitised inhibitory dopamine-D2-autoreceptor (D2-AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age-dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L-type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age-and calciumdependent activity-control of SN DA neurons and its pharmacological modulation.

- by Terrance P Snutch and +1
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- Parkinson's Disease, Dopaminergic Neurotransmision

Human society is strongly rooted in people's experiences of agency; that is, the pervasive feeling that one engages in voluntary behavior and causes one's own actions and resulting outcomes. Rewards and positive affect play an important role in the control of voluntary action. However, the role of positive reward signals in the sense of agency is poorly understood. This study examined effects of reward-related information on the sense of agency by employing the intentional binding paradigm. This paradigm measures the extent to which actions and their effects subjectively shift together across time, reflecting a crucial component of people's sense of agency. Results showed that intentional binding is stronger when participants are primed with reward-related information via brief exposure to positive pictures. Interestingly, this positive priming effect was moderated by baseline eye-blink rates (an indirect marker of striatal dopaminergic functioning); reward-related information increased intentional binding mainly for participants displaying higher baseline eye-blink rates. These findings suggest a possible role for striatal dopamine activity in the process by which reward-related information shapes the way people see themselves as agents.

- by Erik Bijleveld
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- Dopaminergic Neurotransmision, Intentional binding, Reward

The diagnostic nomenclature of bipolar affective dysfunction is distinguished from unipolar mood dysfunction by the presence of mania. The bipolar disorder criteria reflect the current psychiatric understanding of manic-depressive illness... more

- by José Manuel Castellano Jiménez
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- Dopaminergic Neurotransmision, Learning, Motivation, Dopamine

ABSTRACT: Courtesy of its free energy formulation, the hierarchical predictive processing theory of the brain is often claimed to be a grand unifying theory. To test this claim, we consider a central case: reward-related activity of mesocorticolimbic dopaminergic (DA) systems. After reviewing the three most prominent hypotheses of DA activity—the anhedonia, incentive salience, and reward prediction error hypotheses—we conclude that current evidence vindicates explanatory pluralism, while leaves unwarranted the grand unifying claims of the predictive processing theory of the brain. More generally, we suggest that scientific progress in the cognitive sciences is unlikely to come in the form of a single overarching grand unifying theory.

ABSTRACT: This chapter argues that appeals to actual scientific practice show that higher-level psychological explanations are not precluded by reductive explanation, much less rendered extinct. To exemplify this conclusion, the case of... more

Glycine is known as an inhibitory neurotransmitter in the spinal cord and forebrain but its precise role in the forebrain is largely overlooked. This investigation evaluated whether glycine alters acetylcholine, glutamate or dopamine release from striatal tissue using an in vitro approach. We observed that while glycine induced a robust 3 H-acetylcholine release ( 3 H-ACh) from superfused striatal tissue, it failed at releasing 3 H-glutamate or 3 H-dopamine.

- by Lanfranco R P Troncone
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- Dopaminergic Neurotransmision, Dopamine, Striatum, Acetylcholine

ABSTRACT: This paper employs a case study from the history of neuroscience—brain reward function—to scrutinize the inductive argument for the so-called 'Heuristic Identity Theory' (HIT). The case fails to support HIT, illustrating why other case studies previously thought to provide empirical support for HIT also fold under scrutiny. After distinguishing two different ways of understanding the types of identity claims presupposed by HIT and considering other conceptual problems, we conclude that HIT is not an alternative to the traditional identity theory so much as a relabeling of previously discussed strategies for mechanistic discovery.

- by Cory Wright and +1
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- Neuroscience, Psychology, Philosophy of Mind, Philosophy of Science

The advent of neurochemical brain imaging methods has provided an opportunity to study the neurochemistry of the human brain in normal and abnormal development. The aim of this article is to provide an update on recent major developments in neurochemical imaging in schizophrenia research. In this concise review, we discuss the major findings on three neurotransmitters, namely dopamine, serotonin and glutamate. The most promising radioligand for D2/D3 neuroreceptor imaging is the agonist [ 11 C]PHNO, with higher in vivo affinity for D3 than D2 receptors, which can be used to measure amphetamine-induced release of dopamine, and therefore a potential model of dopaminergic alterations in schizophrenia. Recent development of selective radiotracers allow imaging of the serotonin transporter (SERT) using positron emission tomography (PET) with selective tracers such as [ 11 C]DASB. Additionally, the glutamatergic hypothesis has evolved from theory to phase III clinical trials of newer agents with novel mechanisms. With the development of newer radioligands and the in vivo application of magnetic resonance spectroscopy (MRS) at relatively high magnetic field strengths, there is ample scope for further neuroimaging advances.

- by Peter Herscovitch and +2
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- Genetics, Neuroscience, Abnormal Psychology, Biological Psychology

Novelty seeking refers to the tendency of humans and animals to explore novel and unfamiliar stimuli and environments. The idea that dopamine modulates novelty seeking is supported by evidence that novel stimuli excite dopamine neurons and activate brain regions receiving dopaminergic input. In addition, dopamine is shown to drive exploratory behavior in novel environments. It is not clear whether dopamine promotes novelty seeking when it is framed as the decision to explore novel options vs. the exploitation of familiar options. To test this hypothesis, we administered systemic injections of saline or GBR-12909, a selective dopamine transporter (DAT) inhibitor, to monkeys and assessed their novelty seeking behavior during a probabilistic decision making task. The task involved pseudorandom introductions of novel choice options. This allowed monkeys the opportunity to explore novel options or to exploit familiar options that they had already sampled. We found that DAT blockade increased the monkeys’ preference for novel options. A reinforcement learning (RL) model fit to the monkeys’ choice data showed that increased novelty seeking following DAT blockade was driven by an increase in the initial value the monkeys assigned to novel options. However, blocking DAT did not modulate the rate at which the monkeys learned which cues were most predictive of reward or their tendency to exploit that knowledge. These data demonstrate that dopamine enhances novelty-driven value and imply that excessive novelty seeking—characteristic of impulsivity and behavioral addictions—might be caused by increases in dopamine, stemming from less reuptake.

- by Vincent D . Costa
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- Neuroscience, Psychology, Information Science, Decision Making

Dopaminergic drugs frequently produce paradoxical effects depending on baseline performance levels, genotype, or personality traits. The present study for the first time aimed to specify the mechanisms underlying such opposite effects using the following recently reported scenario as an example: depending on the personality trait agentic extraversion (agentic facet, aE; i.e., assertiveness, dominance, ambition, positive emotionality) the selective dopamine D2 receptor antagonist sulpiride (200 mg) had opposite effects on resting posterior vs. anterior theta activity in the electroencephalogram (EEG). In order to better describe these opposite pharmaco-EEG effects and to generate hypotheses regarding the underlying mechanisms, we measured the EEG intermittently over 5 h in 80 healthy male volunteers extremely high or low in aE who had received either placebo or one of three doses of sulpiride (50, 200, or 400 mg). The findings suggest a model postulating stronger pre-vs. postsynaptic subreceptor effects in high aE individuals compared to low aE individuals. Future studies may now systematically apply the model to other examples of paradoxical dopaminergic drug effects and examine the molecular basis of individual differences in pre-vs. postsynaptic dopamine D2 subreceptor sensitivities and densities.

- by Mira Chavanon
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- Bioinformatics, Life Sciences, EEG, Dopaminergic Neurotransmision

Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the cooccurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders.

- by Adrian A Chrobak and +1
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- Dopaminergic Neurotransmision, Dopamine, Electrical Stimulation, Vagus Nerve Stimulation

The molecular underpinnings of exploration and its link to learning and memory remain poorly understood. Here we show that inducible, modest overexpression of neuronal calcium sensor 1 (Ncs1) selectively in the adult murine dentate gyrus (DG) promotes a specific form of exploratory behavior. The mice also display a selective facilitation of longterm potentiation (LTP) in the medial perforant path and a selective enhancement in rapid-acquisition spatial memory, phenotypes that are reversed by direct application of a cell-permeant peptide (DNIP) designed to interfere with NCS-1 binding to the dopamine type-2 receptor (D2R). Moreover, the DNIP and the D2R-selective antagonist L-741,626 attenuated exploratory behavior, DG LTP, and spatial memory in control mice. These data demonstrate a role for NCS-1 and D2R in DG plasticity and provide insight for understanding how the DG contributes to the origin of exploration and spatial memory acquisition.

- by Bechara Saab and +1
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- Neurobiology of Learning and Memory, Dopaminergic Neurotransmision, Synaptic Plasticity, Curiosity

Modern neuroimaging techniques have made a significant contribution to our understanding of human brain and its regulatory mechanisms. These techniques however are limited by their ability to detect only a few dimensions of the brain physiology. There is therefore a need to expand the scope of neuroimaging to allow detection of all known dimensions of the brain activity. There is also a need to explore newer dimensions that affect and regulate brain function. Lastly, the focus of studied on the brain disorders is often directed to symptoms or syndromes which prevents us from understanding real neuropathology. There is therefore a need to change the approach and study brain disorders using neuroscientific techniques, psychological concepts, and philosophical vision. Editorial Rapid advancement in neuroimaging techniques in recent years has presented us with an incredible opportunity to study structure and function of live human brain in almost real time. Using these techniques, we can now visualize fine details of the brain anatomy, track neuronal connectivity and measure task-induced changes in hemodynamics, electric potentials and neurotransmitter concentration. These techniques have empowered us to study not only the structure but also different aspects of the brain function. This empowerment gives us hope that finally we will be able to understand complexities of the nervous system. In the past two decades neuroimaging data have helped us make significant advances in this direction. With these advances we now have better insight about disorders of the nervous system. We are however far from understanding many of these disorders, particularly those that present with psychiatric or psychosomatic symptoms.

- by Rajendra D Badgaiyan
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- Neurology, Psychiatry, Neuroimaging, Dopaminergic Neurotransmision

Multiple mechanisms likely contribute to neuronal death in Parkinson's disease (PD), including mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1a) positively regulates the expression of genes required for mitochondrial biogenesis and the cell's antioxidant responses. Also, expression of PGC-1a-regulated genes is low in substantia nigra (SN) neurons in early PD. Thus upregulation of PGC-1a is a candidate neuroprotective strategy in PD. Here, an adeno-associated virus (AAV) was used to induce unilateral overexpression of Pgc-1a, or a control gene, in the SN of wild-type C57BL/6CR mice. Three weeks after AAV administration, mice were treated with saline or MPTP. Overexpression of Pgc-1a in the SN induced expression of target genes, but unexpectedly it also greatly reduced the expression of tyrosine hydroxylase (Th) and other markers of the dopaminergic phenotype with resultant severe loss of striatal dopamine. Reduced Th expression was associated with loss of Pitx3, a transcription factor that is critical for the development and maintenance of dopaminergic cells. Expression of the neurotrophic factor Bdnf, which also is regulated by Pitx3, similarly was reduced. Overexpression of Pgc-1a also led to increased sensitivity to MPTP-induced death of Th+ neurons. Pgc-1a overexpression alone, in the absence of MPTP treatment, did not lead to cell loss in the SN or to loss of dopaminergic terminals. These data demonstrate that overexpression of Pgc-1a results in dopamine depletion associated with lower levels of Pitx3 and enhances susceptibility to MPTP. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1a in PD. Citation: Clark J, Silvaggi JM, Kiselak T, Zheng K, Clore EL, et al. (2012) Pgc-1a Overexpression Downregulates Pitx3 and Increases Susceptibility to MPTP Toxicity Associated with Decreased Bdnf. PLoS ONE 7(11): e48925.

- by Caroline Bass
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- Neuroscience, Gene Therapy, Dopaminergic Neurotransmision, Oxidative Stress

Medication non-adherence is a great challenge in the treatment of psychotic disorders. Several factors leading to medication
non-adherence in schizophrenia have been identified: drug side-effects, lack of illness insight, negative attitude of the patient and
friends/relatives toward medication, stigma of mental illness and taking medication, poor therapeutic alliance, substance abuse, and
role of the illness in maintaining the family system.
In this work I propose a new vista on the phenomenon of medication non-adherence in psychosis. Rather rule than exception,
non-adherence is to be expected in psychosis, it can be considered as a symptom of psychosis similarly as substance craving and use
are symptoms of the substance use disorders. Relying on the last refinements of the concepts of boredom, anticipatory anhedonia,
intrinsic motivation, and thrill I assume that there is a lure of psychotic episode. In order to escape an extremely unpleasant and
distressing experience of boredom and to experience the thrill of psychosis, the patients are prone to quit antipsychotic therapy.
The phenomena of boredom and the thrill of psychosis are evident but unexploited for strengthening the therapeutic adherence.
Making the lure of psychosis an explicit reason for medication non-adherence would bring to the awareness a personal choice
between short-term pleasure of the psychotic thrill and prevention of long-term losses due to a psychotic episode. Neurobiological
and psychobiological underpinning of the psychotic thrill has been suggested. An explanation of the pleasure of psychosis and
substance use, which overcomes the circular explanation of reward in which dopamine appears as the cause and consequence of
reward, has been proposed.
The present synthesis can be regarded as a contribution to the field of theoretical psychiatry. It points to a chance for psychiatry
to do more for patients’ wellbeing and treatment adherence performing in a new key – dealing with boredom and pleasure in
patients’ everyday life.

- by Sasa Brankovic
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- Psychiatry, Psychosis, Motivation (Psychology), Schizophrenia

Iron (F e) is an important metal to the organism homeostasis and exists abundantly in
the environment. Moderate levels of Fe obtained from food are necessary for normal
cell physiology; however, abnormally high levels of Fe may have toxic effects by
reducing H2O2 to the highly cytotoxic hydroxyl radical (OH•) (Fenton catalysis). Fe is
ubiquitous toxicant to the environment and also widely used in food products, however
its effects to the nervous system are not well understood. Herein, we evaluated the toxic
effects of Fe using C. elegans and investigated various parameters in order to contribute
to the understanding of Fe-induced toxicity and to validate this model. Our goal was to
search for therapeutic targets that are more effective than those currently used. The Fe
LD50 of acute exposure (30 min) was 1.2 mM, and we verified that worms readily take
up this metal. Furthermore, sublethal Fe concentrations significantly decreased the
worms’ lifespan and brood size compared to non-exposed worms. We also observed that animals exposed to Fe had decreased locomotor activity and decreased mechanic
sensitivity, suggesting possible dysfunction of the nervous system. In agreement, we
found cholinergic and dopaminergic alterations in the worms. In summary, we suggest
that Fe leads to selective neuronal damage, which might be the underlying cause of altered behavior and reproductive defects.

An explorative review of literature of pharmacological aspects of acetylcholine (ACh) and dopamine (DA) neurotransmitter systems on the methods of causation of motor dysfunction, ranging from dyskinesia to tremulous jaw movements. The current author comments on the ACh system with reference to nicotinic ACh receptor (nAChR) blockade, competitive antagonism and tacrine-induced jaw tremor research. The DA system implication is also reviewed and raises current topical issues models of neuro-circuitry and ACh-DA interactions. To conclude, the ACh and DA systems and their interactions require future research to establish concrete mechanisms and the complexities of these system interactions to be explored in relation to dysfunctional motor behaviour.

- by Nora S Vyas and +2
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- Genetics, Neuroscience, Abnormal Psychology, Biological Psychology

Cathinones are a class of drugs used to treat various medical conditions including depression, obesity, substance abuse, and muscle spasms. Some "designer" cathinones, such as methcathinone, mephedrone, and methylone, are used nonclinically for their stimulant or entactogenic properties. Given the recent rise in nonmedical use of designer cathinones, we aimed to improve understanding of cathinone pharmacology by investigating analogs of methcathinone with a CF3 substituent at the 2-, 3 , or 4-position of the phenyl ring (TFMAPs). We compared the TFMAPs with methcathinone for effects on monoamine uptake transporter function in vitro and in vivo, and for effects on locomotor activity in rats. At the serotonin transporter (SERT), 3-TFMAP and 4 TFMAP were 10-fold more potent than methcathinone as uptake inhibitors and as releasing agents, but 2 TFMAP was both a weak uptake inhibitor and releaser. At the norepinephrine and dopamine transporters (NET and DAT), all TFMAP isomers were less potent than methcathinone as uptake inhibitors and releasers. In vivo, 4-TFMAP released 5-HT, but not dopamine, in rat nucleus accumbens and did not affect locomotor activity, whereas methcathinone increased both 5-HT and dopamine and produced locomotor stimulation. These experiments reveal that TFMAPs are substrates for the monoamine transporters and that phenyl ring substitution at the 3- or 4-position increases potency at SERT but decreases potency at NET and DAT, resulting in selectivity for SERT. The TFMAPs might have therapeutic value for a variety of medical and psychiatric conditions and may have lower abuse liability compared to methcathinone due to their decreased DAT activity.

- by Nicholas V Cozzi, Ph.D. and +1
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- Drug Designing, Neuropharmacology, Dopaminergic Neurotransmision, Serotonin Transporter

Some patients with advanced Parkinson's disease (PD) develop dose-related fluctuations in mood. This may reflect alterations in dopamine-influenced brain circuits that mediate emotion. However, there is no available information to localize which dopamineinfluenced neurons may be most affected. Eight patients with PD and clinically significant levodopa-related mood fluctuations (mania, depression, or anxiety) were compared to 13 patients with similarly severe PD and fluctuations of motor function but not of mood. Regional cerebral blood flow (rCBF) was measured with positron emission tomography before and after levodopa (in the presence of carbidopa). The rCBF response to levodopa in medial frontal gyrus and posterior cingulate cortex (PCC) significantly differed between mood fluctuators and control patients (corrected po0.02). Other regions with uncorrected po0.001 in this comparison were cortical Brodmann areas 22, 40, 13, 11, and 28, hippocampus, and claustrum. The levodopa activation paradigm detected group differences not evident in a comparison of resting rCBF. Abnormalities of dopamine innervation may produce mood fluctuations via effects on PCC, an area strongly linked to mood and anxiety and with known rCBF responsiveness to levodopa or D2-like dopamine receptor agonists. We speculate that mood fluctuations may arise in parkinsonian patients who have abnormal dopaminergic modulation of caudate nucleus, anterior cingulate cortex, or orbital frontal cortex, all of which innervate PCC. The findings require confirmation in larger and bettermatched groups.

- by Tamara Riley
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- Psychopharmacology, Neuroimaging, Depression, Schizophrenia

Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients’ conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood–brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.

- by Alberto Vazquez and +2
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- Immunology, Sensors and Sensing, Brain Imaging, Traumatic Brain Injury