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

2025, Movement Disorders

BackgroundThe objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD).MethodsThirty‐five participants were randomly allocated to a 36‐session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation‐evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS‐UPDRS part III, finger tapping, Timed‐up‐and‐go) and nonmotor assessments (Starkstein Apathy Scale,...

2025, Working Paper

This manuscript is a preprint hypothesis paper exploring a theoretical link between rejection-sensitive dysphoria, interoception, and Takotsubo syndrome. It has not yet been peer reviewed. This preprint proposes a novel hypothesis... more

2025

Oxidative stress is considered a significant contributor to cellular damage, which may accumulate and result in cellular and organism senescence and death. Oxidative stress and damage have been correlated with a number of central nervous system (CNS) disorders in mammals, like Alzheimer’s and Parkinson’s diseases. Using the model organism Caenorhabditis elegans, the current study investigates the survival of mutant C. elegans strains under oxidative stress. Using strains containing mutations in the glr-1 and nmr-1 genes encoding subunits of ionotropic glutamate receptors, we found no significant differences of survival among wild type (WT) and glutamate receptor mutants, though prior research has suggested the involvement of glutamatergic neurons in antioxidant defenses. Abbreviations: AMPA ‐ Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid; NMDA ‐ N-methyl-D-aspartate; ROS ‐ Reactive oxygen species; WT ‐ wild type

2025, European Journal of Pharmacology

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 CF 3 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 a 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.

2025, Neuropsychology Review

Multiple theories of Attention-Deficit/Hyperactivity 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

2025

Family-based association analysis of alcohol dependence

2025

Reichborn-Kjennerud 1envisages mind and brain as inhabiting the same skull, now while this would not necessarily be challenged by most people it is by Neurology and Psychiatry which hold that only the physical is to be trusted, the mind is merely an abstract waiting for proof on its actual physical self, if indeed it exists at all. The trouble is that any understanding of this part of the human anatomy is on slippery ground. For the two mentioned groups, the brain can only be understood materially as this confirms their science. For them, the world is a material formation and from that position, difficulties occur. The Mind while connected to the brain , as it seems one is impossible without the other, consciousness sometimes given a pass as merely a necessary action in order to sustain other operations, that is with decision making properties. These rejections of two evident operating paradigms and thereby the host of activities normally associated with them, operations that extent beyond procedural activities , provide other reasons as to why psychiatry is not genuine. Gunnar perceives consciousness as removed from brain processes and observing such processes. Both of the disciplines above see only the physical nature of the brain as evident in the fashion of what you see is what you get. Visibility is everything. And yet their models indicate no concern for other known aspects, which we suppose make us human. My concept of reflective looping, which has similarities to Gunner's ideas, allows the possibility that by entwining with the environment, especially our made environment, we created ourselves and through the symbolic nature of our environment we continue to do so. Our cluttering of the spaces around us indicates that.

2025, Molecular Psychiatry

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers o...

2025

In this paper we present computational model based on first principles with the purpose to study the behavior of biological neural networks. A network is constructed using as elementary building blocks DLA clusters, a structure well known in solid state physics, giving thus the network spatial structure, and in this way differentiating the model from most previous studies in this field. The blocks are paced randomly on 2D-space and synapses are formed where neighboring blocks overlap. The behavior of the network is studied, focusing not only on signal transmission and analysis, but also on the results of synapse loss, common in biological systems under certain diseases, such as Alzheimer's and Parkinson's. The network's response follows the same basic characteristics as real biological systems under similar circumstances, and the importance of the spatial structure of the network in this behavior is examined..

2025

Mental health disorders represent a significant public health concern globally. With the increasing burden of psychiatric conditions such as depression, schizophrenia, and bipolar disorder, there is a growing interest in understanding the genetic underpinnings of these illnesses. This paper explores the role of genetics in mental health through an interdisciplinary bioscience lens, emphasizing recent genome-wide association studies (GWAS), the heritability of psychiatric conditions, and gene-environment interactions. Integrating insights from genetics, neuroscience, and psychology, this research underscores the necessity of a holistic approach to psychiatric genetics. Understanding genetic contributions not only aids early diagnosis and personalized treatment but also shapes public health strategies to reduce stigma and improve mental healthcare delivery.

2025, The Israel journal of psychiatry and related sciences

The specific pathogenesis of increased vulnerability to cocaine-induced paranoia/psychosis is unknown. Weight loss has been long observed in patients abusing stimulants (including cocaine and the amphetamines). In the current study, we compared Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) in Cocaine-Induced Psychosis cases, referred to as "Cocaine-Induced Psychosis-prone" (n=40) and non-Cocaine-Induced Psychosis cases, referred to as "Cocaine-Induced Psychosis-resistant" (n=29) consecutively admitted to a research substance abuse unit to determine whether Body Mass Index is associated with Cocaine-Induced Psychosis. Height and weight were measured and Body Mass Index calculated by a licensed nutritionist using a standardized protocol. Cocaine-induced psychosis and cocaine use patterns were assessed using the Cocaine Experience Questionnaire. Body Mass Index in the Cocaine-Induced Psychosis-prone patients was signif...

2025, PLOS ONE

Inattention and distractibility are core symptoms of attention deficit hyperactivity disorder (ADHD). Still the neuronal organization is largely unknown. Previously we studied the electrophysiological activity of a distinct neuronal network-the retina-and found no change in stimulus-driven neural activity in patients with ADHD. However there is growing evidence for an elevated non stimulus-driven neural activity, or neuronal background noise, as underlying pathophysiological correlate. To further examine the biological bases that might underlie ADHD and problems with inattention, we performed a new analysis to test the hypothesis of an elevated background noise as underlying neuronal correlate for ADHD and problems with inattention in humans. A direct measure of background noise in patients with ADHD has not been described yet. The retinal background noise was assessed based on pattern electroretinogram (PERG) data in 20 unmedicated ADHD patients and 20 healthy controls. The PERG is an electrophysiological measure for retinal ganglion cell function. ADHD severity was assessed by interview and questionnaire.

2025, Croatian Medical Journal

To perform a comprehensive evaluation of association of common genetic variants in candidate genes in the dopaminergic pathway with schizophrenia in a sample from Croatian population. Methods A case-control association study was performed on 104 unrelated patients with schizophrenia recruited from a psychiatric hospital in Zagreb and 131 phenotypically normal Croatian subjects. Forty-nine tagging single nucleotide polymorphisms (tagSNPs) in 8 candidate genes in the dopaminergic pathway were identified from the HapMap database and tested for association. Genotyping was performed using the SNPlex platform. Statistical analysis was conducted to assess allelic and genotypic associations between cases and controls using a goodness of fit χ 2 test and trend test, respectively; adjustment for multiple testing was done by permutation based analysis. Significant allele frequency differences between schizophrenia cases and controls were observed at 4 tag-SNPs located in the genes DRD5, HTR1B1, DBH, and TH1 (P < 0.005). A trend test also confirmed the genotypic association (P < 0.001) of these 4 tagSNPs. Additionally, moderate association (P < 0.05) was observed with 8 tagSNPs on SLC6A3, DBH, DRD4, SLC6A4, and COMT. Conclusions Common genetic variants in genes involved in the dopaminergic pathway are associated with schizophrenia in the populations of Caucasian descent.

2025, Frontiers in Neurorobotics

2025

This brief report presents a narrative literature review describing potential pathogenetic mechanisms underlying the transformation of drug-induced psychoses into chronic psychotic disorders of the schizophrenic spectrum. The central role of hyperdopaminergia in the development of productive psychotic symptoms is discussed, along with the possibility of dopamine D2 receptor sensitization resulting from prolonged use of stimulant drugs. Attention is drawn to the previously described phenomenon of reverse tolerance, the study of which at genetic, molecular, neurotransmitter, and clinical levels may offer a promising approach for clinical assessment of prognosis and prevention of schizophrenia in individuals with a history of substance use.

2025, Espejos en el abismo

Horizonte, cielo y tierra en un abrazo imposible, yace el abismo de la ilusión. Caminamos hacia él, creyendo que el suelo es eterno. A cada paso que damos, nos acerca a la orilla de lo desconocido. Las ilusiones son espejismos en el desierto de la mente, promesas que desaparecen cuando te acercas. El verdadero desafío es aprender a navegar entre ellas, lo que parece real no es más que un abismo distorsionado. Elige tus ilusiones sabiamente, porque algunas son trampas que te arrastran al vacío mientras que otras son puentes que te llevan a la verdad. PÁG. 3 Existen diferentes vías dopaminérgicas: Vía mesolímbica: Asociada con el placer y la recompensa. Vía nigroestriatal: Control del movimiento. La deficiencia de dopamina en esta vía está relacionada con la enfermedad de Parkinson. Vía mesocortical: Involucrada en funciones cognitivas y emocionales. Desequilibrios en los niveles de dopamina están relacionados con adicciones, esquizofrenia y trastornos del movimiento. Producida en el tronco encefálico (núcleos del rafe). Regula el estado de ánimo, el sueño, el apetito y la percepción del dolor. Los inhibidores selectivos de la recaptación de serotonina (ISRS) se utilizan para tratar la depresión y la ansiedad. Regula la alerta, el estado de ánimo y las respuestas al estrés. Actúa en el sistema nervioso autónomo para controlar funciones como la frecuencia cardíaca y la presión arterial. Asociada con la respuesta de "lucha o huida". Estimula el sistema cardiovascular y aumenta la disponibilidad de energía. Sustancia P Involucrada en la transmisión del dolor en la médula espinal. También desempeña roles en la inflamación y las respuestas al estrés.

2025

Humans and other animals often engage in activities for their own sakes rather than as steps toward solving practical problems. Psychologists call these intrinsically motivated behaviors. What we learn during intrinsically motivated behavior is essential for our development as competent autonomous entities able to efficiently solve a wide range of practical problems as they arise. In this paper we present initial results from a computational study of intrinsically motivated learning aimed at allowing artificial agents to construct and extend hierarchies of reusable skills that are needed for competent autonomy. At the core of the model are recent theoretical and algorithmic advances in computational reinforcement learning, specifically, new concepts related to skills and new learning algorithms for learning with skill hierarchies.

2025

Background and aim: Attention deficit hyperactivity disorder (ADHD) is heterogeneous neurobehavioral disorders that co-exist with cognitive and learning deficits affecting 3-7% of children. We study the role of rosemary in the protection of the prefrontal cortical neurons against rotenone-induced ADHD in juvenile rats. Methods: Twenty-four juvenile rats were divided into four groups (n=6): control group, received olive oil 0.5 ml/kg/day/ I.P. for 4 weeks, rosemary group received rosemary 75 mg/kg/day/ I.P. for 4 weeks, rotenone group received rotenone 1 mg/kg/day/ I.P. dissolved in olive oil for 4 days and combined group received rotenone 1 mg/kg/day/ I.P. for 4 days and rosemary 75 mg/kg/day/ I.P. for 4 weeks. Results: Rotenone group showed higher impulsivity with reduction in the recognition index and total locomotor activity. However, combined group showed significant improvement in the recognition index and the total locomotor activity. Neurochemical analysis disclosed that rotenone decreased levels of GSH and significantly increased lipid peroxidation and oxidative stress. The administration of rosemary amended these neurochemical changes. Rotenone caused a significant increase in serum amyloid protein A and C-reactive protein levels indicating a marked state of inflammation. Rosemary ameliorated these biochemical changes. The immunohistochemical expression of tyrosine hydroxylase was decreased in the rotenone group. On the other hand, caspase-3 was increased in the rotenone group. PCR confirmed immunohistochemical results for gene expression. Conclusions: The findings of the behavioral, neurochemical, biochemical, immunohistochemical and molecular outcomes suggested that rosemary could fight oxidative stress, inflammation and apoptosis in the prefrontal cortex of rotenone-induced ADHD in juvenile rats. (www.actabiomedica.it)

2025, The British journal of psychiatry : the journal of mental science

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain ...

2025, Academia Biology

Altered cognitive, social, and emotional behaviors are early-onset symptoms of Parkinson’s disease (PD) associated with the partial loss of dopamine (DA) neurotransmission in the nucleus accumbens (n.Acc). A partial 6-hydroxydopamine (OHDA) bilateral lesion of the dorsal striatum (DS) in rats induces impairments in cognitive functions, social behavior, and depressive-like behavior, with little effect on locomotor activity, whether spontaneous or forced. Limited data are available on n.Acc dopaminergic neurotransmission in these lesioned animals, under resting and nicotine-stimulated conditions. In our study, rats with bilateral 6-OHDA-lesioned DS showed a 44–59% decrease in DS catecholamine content and about a 32% decrease in ventral tegmental area/substantia nigra tyrosine hydroxylase–positive neurons compared with sham-operated animals. No motor coordination impairment was detected by the rotarod test, and the basal DA release in n.Acc, tested by microdialysis, did not differ among lesioned, sham, and naïve rats. In lesioned animals, however, subcutaneous (s.c.) saline injection caused a decrease in DA release in n.Acc, confirming a threshold reduction in DA function in lesioned animals. Nicotine increased DA release in the n.Acc of naïve rats, with a maximally effective dose of 0.32 mg/kg s.c. This nicotine treatment restored DA release in the n.Acc of lesioned animals without affecting DS total catecholamine content. These data demonstrate the functionality of surviving DA neurons in the n.Acc (shell part) after partial lesion and suggest the relevance of the proposed model for the neurochemical characterization of early interventions in PD.

2025, Neuropsychology Review

2025, Frontiers in Integrative Neuroscience

Introduction: Adversities during the perinatal period can decrease oxygen supply to the fetal brain, leading to various hypoxic brain injuries, which can compromise the regularity of brain development in different aspects. To examine the catecholaminergic contribution to the link between an early-life hypoxic insult and adolescent behavioral aberrations, we used a previously established rat model of perinatal hypoxia but altered the hypobaric to normobaric conditions. Methods: Exploratory and social behavior and learning abilities were tested in 70 rats of both sexes at adolescent age. Inherent vertical locomotion, sensorymotor functions and spatial learning abilities were explored in a subset of animals to clarify the background of altered exploratory behavior. Finally, the concentrations of dopamine (DA) and noradrenaline in midbrain and pons, and the relative expression of genes for DA receptors D1 and D2, and their downstream targets (DA-and cAMP-regulated phosphoprotein, Mr 32 kDa, the regulatory subunit of protein kinase A, and inhibitor-5 of protein phosphatase 1) in the hippocampus and thalamus were investigated in 31 rats. Results: A lesser extent of alterations in exploratory and cognitive aspects of behavior in the present study suggests that normobaric conditions mitigate the hypoxic injury compared to the one obtained under hypobaric conditions. Increased exploratory rearing was the most prominent consequence, with impaired spatial learning in the background. In affected rats, increased midbrain/pons DA content, as well as mRNA levels for DA receptors and their down-stream elements in the thalamus, but not the hippocampus, were found. We can conclude that a mild hypoxic event induced long-lasting disbalances in mesothalamic DA signaling, contributing to the observed behavioral alterations. The thalamus was thereby indicated as another structure, besides the well-established striatum, involved in mediating hypoxic effects on behavior through DA signaling.

2025, Iranian journal of public health

Happiness underlying factors are considerable from two dimensions: endogenic factors (biological, cognitive, personality and ethical sub-factors) and exogenic factors (behavioral, socialcultural, economical, geographical, life events and aesthetics sub-factors). Among all endogenic factors, biological sub-factors are the significant predictors of happiness. Existence of significant differences in temperament and happiness of infants is an indicator of biological influences. Therefore, this study aimed to consider biological factors that underlie happiness. At the first, all of the biological factors in relation with happiness were searched from following websites: PubMed, Wiley& Sons, Science direct (1990-2014). Then, the articles divided into five sub-groups (genetic, brain and neurotransmitters, endocrinology and hormones, physical health, morphology and physical attractiveness). Finally, a systematic review performed based on existing information. Results of studies on genetic fa...

2025, Brain Research Bulletin

2024

The capacity of re-using previously acquired skills can greatly enhance robots' learning speed and behavioral complexity. 'Intrinsically Motivated Reinforcement Learning (IMRL)' is a framework that exploits this idea and proposes to build agents capable of solving several specific tasks by assembling general-purpose building-block behaviors ('skills') previously acquired on the basis of 'intrinsic motivations'. This paper proposes a novel neural-network hierarchical reinforcement-learning architecture which exploits 'evolutionary robotics (ER)' techniques that not only allow tackling important limits of IMRL, as shown in previous papers, but they also allow investigating two other important issues, namely: (1) the optimization of the parameters that regulate the architecture's learning processes; (2) the optimization of the time the architecture dedicates to the acquisition of the skills' repertoire. These two issues are investigated here through a simulated robot engaged in solving compositional path-following navigation tasks. The results obtained indicate that the proposed approach allows obtaining a remarkable improvement of performance of the architecture, while at the same time decreasing the time the system needs to learn the skills, with respect to cases where hand-tuned parameters are used.

2024, European Neuropsychopharmacology

substance use and psychiatric disorder. Among them, the most associated were related to immune system and rRNA processing (p-values o 0.001). Besides, within the top 15 differentially expressed genes, most of them were previously associated with mental illness, substance abuse and dependence (for example, CCR3, and CHST7). Discussion: Although, we found an association between emotional disorders and substance abuse, we cannot say whether this is a cause or consequence. The understanding of the biological alterations that trigger the psychiatric disorders and their association with substance abuse, might help to develop prevention strategies to psychiatric disorders and avoid substance abuse. Furthermore, we found no substance abusers with ADHD which may be related with their age (very young individuals). Although we have found no significant co-expression network, we identified 18 pathways as well as 2 biological processes related to immune system, rRNA processing, among others. Therefore, our results suggest that these pathways could be associated with substance abuse in adolescents. It is also worth to mention that our cohort is a very well clinically characterized and unique sample of adolescents with psychiatric disorders and healthy controls, and we are running next year the 3rd year follow up which may increase the sample size of substance abuser and individuals with psychiatric disorders.

2024, Malaysian Journal of Medicine and Health Sciences

Introduction: Dopamine receptor type 2 gene (DRD2 Taq1A, Taq1B and Taq1D) and psychosocial factors such as eating behaviour and physical activity engagement have been demonstrated by past studies, to impact obesity, and eventually affect health status and quality of life. However, personality traits were largely examined as a direct or indirect risk factor for obesity with inconclusive results. Hence, this study investigates the predictive effect of Five Factor personality traits on psychosocial factors related to obesity (i.e., level and motives of physical activity, and eating behaviour) besides examining the association of Five Factor personality traits with DRD2 genotypes. Materials and methods: 394 participants (125 males and 269 females) from Universiti Tunku Abdul Rahman (UTAR), Malaysia participated in this study, which involved obtaining anthropometric measurements, mouthwash samples and responses across three scaled items. A genotypic and allelic variance of the DRD2 Taq1 gene was conducted by examining the Restriction Fragment Length Polymorphism using the PCR method. Results: In the eating behaviour domain, Conscientiousness, Extraversion and Neuroticism significantly predicted Uncontrolled Eating (UE) and Emotional Eating (EE). In the physical activity domain, Extraversion positively predicted Total IPAQ score. Conscientiousness, Extraversion and Agreeableness significantly predicted motives for physical activity. The genotypic and allele analysis results showed that participants with higher Neuroticism were significantly different on the ANKK1/DRD2 Taq1A and DRD2 Taq1B. Conclusion: Personality traits could be an aspect to be incorporated into tailoring biopsychosocial obesity management programmes.

2024, Journal of Alzheimer's disease & Parkinsonism

Novel neuroimaging technique to study Parkinson's disease D iagnosis of Parkinson's disease is mostly clinical. As a result, it is difficult to make an accurate diagnosis at an early stage. Because of the subjective nature of clinical diagnosis, many patients are misdiagnosed at an early stage. Because of this, treatment gets delayed and the disease progression cannot be slowed down. It is therefore important to have a diagnostic technique that helps us make an early diagnosis. A new imaging technique that we recently developed could be useful. The technique called single scan dynamic molecular imaging technique (SDMIT) uses positron emission tomography (PET) to detect, map and measure dopamine released acutely during a cognitive or behavioral processing. It exploits the competition between dopamine and its receptor ligand for occupancy of the same receptor site. In this technique after patients are positioned in the PET camera, a radio-labeled dopamine ligand is injected intravenously and the PET data acquisition started. These data are used by a receptor kinetic model to detect, map and measure dopamine released dynamically in different brain areas. The patients were asked to perform a behavioral or cognitive task while in the scanner and the amount of dopamine released in different brain areas measured. By comparing this data with data acquired previously in age-matched healthy volunteers during performance of a similar task, it is possible to determine whether dopamine neurotransmission is dysregulated in the patients and whether the dysregulation is responsible for clinical symptoms. Finding of a significant dysregulation in dopamine neurotransmission would confirm diagnosis of Parkinson's disease. Since this technique measures dopamine released under conditions of cognitive and behavioral stress, it can detect changes at a very early stage, when dysregulation of dopamine neurotransmission is not expressed at rest but manifests under conditions of cognitive/behavioral overload.

2024, Current Medical Imaging Reviews

2024, Brain Research

Released dopamine was monitored voltammetrically in the rat striatum in response to electrical stimulation of the nigrostriatal bundle. Stimulation parameters encompassed those typically used in behavioral studies. Dopamine released during intracranial self-stimulation (ICSS)-like stimulation reached a maximum within the first minute of stimulation, then rapidly decreased. The pattern of release obtained with continuous stimulation as a function of current and frequency supports the view that as the stimulation current is increased, a greater number of neurons are stimulated, while increasing the frequency of stimulation results in a fixed population of neurons being stimulated more intensely. Computer modeling of stimulated release from a population of dopaminergic nerve terminals was used to interpret effects of current and frequency and to predict ICSS release patterns as a function of schedule of reinforcement.

2024, Journal of Neuroscience Research

The dopamine D4 receptor 7-repeat allele (D4.7R) has been linked with psychiatric disorders such as attention-deficit–hyperactivity disorder, autism, and schizophrenia. However, the highly diverse study populations and often contradictory findings make it difficult to draw reliable conclusions. The D4.7R has the potential to explain individual differences in behavior. However, there is still a great deal of ambiguity surrounding whether it is causally connected to the etiology of psychiatric disorders. Therefore, humanized D4.7R mice, with the long third intracellular domain of the human D4.7R, may provide a valuable tool to examine the relationship between the D4.7R variant and specific behavioral phenotypes. We report that D4.7R male mice carrying the humanized D4.7R variant exhibit distinct behavioral features that are dependent on the light–dark cycle. The behavioral phenotype was characterized by a working memory deficit, delayed decision execution in the light phase, decreased stress and anxiety, and increased risk behavior in the dark phase. Further, D4.7R mice displayed impaired social recognition memory in both the light and dark phases. These findings provide insight into the potential causal relationship between the human D4.7R variant and specific behaviors and encourage further consideration of dopamine D4 receptor (DRD4) ligands as novel treatments for psychiatric disorders in which D4.7R has been implicated.

2024, NeuroQuantology, 2024, Volume 22, Issue 5, Pages 158-163

Introduction: Sleep is a vital biological process regulated by various neurotransmitter systems, especially dopamine, which plays a critical role in modulating different sleep stages, including REM and NREM phases. Sleep deprivation has been shown to impact neurotransmitter levels, potentially disrupting normal sleep architecture. This study investigates how neurotransmitter systems, particularly the dopaminergic system, influence sleep modulation and recovery after sleep deprivation. Materials and Methods: Fifty healthy male volunteers, aged 20-30 years, were divided into three groups: non-sleep deprived, total sleep deprived (TSD), and REM sleep deprived (RSD). Participants' sleep patterns were monitored using EEG and EMG, and blood samples were collected to assess cortisol, prolactin, and estradiol levels. Dopamine transporter (DAT) activity in the striatum was measured using SPECT imaging. Hormonal changes and DAT availability were analyzed across sleep deprivation and recovery phases. Results: No significant changes were observed in cortisol, prolactin, or estradiol levels immediately after two nights of TSD or four nights of RSD. However, during the recovery phase, estradiol levels positively correlated with slow-wave sleep (SWS) and DAT activity in the striatum, particularly in the TSD group. Prolactin levels correlated with REM sleep latency, indicating neurotransmitters' delayed impact on sleep recovery. Discussion: The findings suggest that while neurotransmitter systems, particularly dopamine, do not exhibit immediate alterations in response to sleep deprivation, they play a critical role during sleep recovery. SPECT imaging revealed that increased DAT activity during recovery correlates with higher estradiol levels, highlighting dopamine's role in promoting deeper, restorative sleep. These results underscore the subtle yet essential influence of neurotransmitter systems in regulating sleep patterns following deprivation. eISSN1303-5150 www.neuroquantology.com Conclusion: This study underscores the critical, though often hidden, role of neurotransmitter systems, especially dopamine, in modulating sleep and recovery after sleep deprivation. While immediate hormonal responses to deprivation are minimal, dopamine plays a crucial role in restoring sleep homeostasis during recovery phases.

2024, International Journal of Medical and Biomedical Studies (IJMBS), Volume 5, Issue 5, May 2021

The Role of the Dopaminergic System in Sleep-Wake Regulation. Material & Methods: The study was conducted at the sleep laboratory of the department of psychobiology with the approval of the ethics Committee of the university as well as the radiation protection center. Fifty healthy male volunteers ranging from 20 to 30 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived). During the week preceding the study as well as during the study period, participants were asked to abstain from alcohol, chocolate, and caffeinated beverages and to maintain a standardized bedtime schedule in accordance with their regular habits. Blood samples were collected every morning from each volunteer during the experimental protocol to evaluate if the sleep deprivation promoted changes in cortisol, prolactin, and estradiol levels (hormones related to dopaminergic activity and stress). Results: (ROIs) for [ 99m Tc] TRODAT-1 were used to estimate the concentration of DAT in the striatum (right and left at baseline) post SD, and post-sleep recovery. An elliptical ROI was placed on three consecutive slices in the occipital cortex, an area used for reference of non-specific DAT binding. The results show that after either 2 nights of total sleep deprivation or 4 nights of selective suppression of rem sleep, there were no statistical differences in prolactin, estradiol, and cortisol levels, as assessed by intra-group analysis. Conclusion: We can't exclude that the hormones assessed did not lose their periodic pattern of excretion during sleep loss. Since the volunteers were injected with a radioactive isotope to perform the speCt, additional blood samples to evaluate hormone levels were not recommended after this intervention.

2024, Neuropsychopharmacology

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.

2024, Brain

Parkinson's disease is characterized by a progressive degeneration of dopaminergic neurons in the midbrain, yet the cause of this neuronal loss is still unknown. It has been hypothesized that Parkinson's disease could be the consequence of accelerated ageing. In order to reveal a possible common process during ageing and Parkinson's disease neurodegeneration, catecholaminergic neurons of five anatomical regions of the brainstem (substantia nigra, central grey substance, ventral tegmental area, periand retrorubral area, and locus coeruleus) have been quantified using immunohistochemical staining for tyrosine hydroxylase (TH) on regularly spaced sections, between the rostral and caudal poles of the mesencephalon and in the rostral pole of the pons, in post-mortem Keywords: substantia nigra; tyrosine hydroxylase; ageing; human Abbreviations: A8 ϭ peri-and retro-rubral catecholaminergic cell group A8; AChE ϭ acetylcholinesterase; CGS ϭ central grey substance; LC ϭ locus coeruleus; SNpc ϭ substantia nigra pars compacta; TH ϭ tyrosine hydroxylase; VTA ϭ ventral tegmental area

2024

The World Congress of Psychiatric Genetics (WCPG) has become an annual event since the early 1990's sponsored by the International Society of Psychiatric Genetics (ISPG). Each year the latest published and unpublished findings are aired for discussion by representatives of the majority of research programs on this topic worldwide. The 2007 congress was held in New York City and attracted over 1000 researchers. The topics emphasized included results from whole genome association studies, the significance of copy number variation and the important contributions of epigenetic events to psychiatric disorders. There were over 20 oral sessions devoted to these and other topics of interest. Young investigator recipients of travel awards served as rapporteurs to summarize sessions and these summaries follow.

2024, Journal of Addiction Research and Therapy

E vidence from clinical, animal, and neuroimaging experiments suggest that the addictive behavior is associated with dysregulated dopamine neurotransmission. Precise role of dopamine in establishment and maintenance of addiction however is unclear. In this context animal studies on the brain reward system and associative memory processing provide a novel insight. It was shown that both processing involve dopamine neurotransmission and are disrupted in addiction. These findings indicate that dysregulated dopamine neurotransmission alters the brain processing of not only the reward system but also that of the memory of association between an addictive substance and reward. These alterations lead to maladaptive motivational behavior leading to addiction. This concept however is based mostly on the data obtained in laboratory animals because of the paucity of human data. Due to lack of a reliable technique to study neurotransmission in the live human brain, it has been a problem to study the role of dopamine in human volunteers. A recently developed dynamic molecular imaging technique however, provides an opportunity to study these concepts in human volunteers because the technique allows detection, mapping and measurement of dopamine released in the live human brain during task performance. Biography Rajendra Badgaiyan completed his M.D. and M.A.

2024, Frontiers in Integrative Neuroscience

2024, The Journal of Physiological Sciences

The external globus pallidus (GP) firing rate synchronizes the basal ganglia-thalamus-cortex network controlling GABAergic output to different nuclei. In this context, two findings are significant: the activity and GABAergic transmis- sion of the GP modulated by GABA B receptors and the presence of the GP-thalamic reticular nucleus (RTn) pathway, the functionality of which is unknown. The functional participation of GABA B receptors through this network in cortical dynamics is feasible because the RTn controls transmission between the thalamus and cortex. To analyze this hypothesis, we used single-unit recordings of RTn neurons and electroencephalograms of the motor cortex (MCx) before and after GP injection of the GABA B agonist baclofen and the antagonist saclofen in anesthetized rats. We found that GABA B agonists increase the spiking rate of the RTn and that this response decreases the spectral density of beta frequency bands in the MCx. Additionally, injections of GABA B antagonists decreased the firing activity of the RTn and reversed the effects in the power spectra of beta frequency bands in the MCx. Our results proved that the GP modulates cortical oscillation dynamics through the GP-RTn network via tonic modulation of RTn activity.

2024, International Journal of Molecular Sciences

The current treatments of Parkinson disease (PD) are ineffective mainly due to the poor understanding of the early events causing the decline of dopaminergic neurons (DOPAn). To overcome this problem, slow progressively degenerating models of PD allowing the study of the pre-clinical phase are crucial. We recreated in a short ex vivo time scale (96 h) all the features of human PD (needing dozens of years) by challenging organotypic culture of rat substantia nigra with low doses of rotenone. Thus, taking advantage of the existent knowledge, the model was used to perform a time-dependent comparative study of the principal possible causative molecular mechanisms undergoing DOPAn demise. Alteration in the redox state and inflammation started at 3 h, preceding the reduction in DOPAn number (pre-diagnosis phase). The number of DOPAn declined to levels compatible with diagnosis only at 12 h. The decline was accompanied by a persistent inflammation and redox imbalance. Significant microglia...

2024, Movement Disorders

Wilson's disease (WD) is an autosomal recessive disorder characterized by the functional disruption of the copper-transporting protein adenosine triphosphatase 7B (ATP-ase 7B). The disease is caused by mutations in ATP7B gene. It seems that the type of mutation in ATP7B only to some degree determines phenotypic manifestation of WD. We examined two pairs of monozygotic twins discordant for WD phenotype. The first set of twins were ATP7B compound heterozygotes c.3207C>A (p.H1069Q)/c.1211_1212insA (p.N404Kfs). The index case developed severe liver failure followed by depressive symptoms, dysarthria, and tremor at the age of 36. Her sister remained presymptomatic at diagnosis at the age of 39. The second twins were ATP7B c.3207C.A (p.H1069Q) homozygotes. The index case presented with dysarthria and tremor at the age of 26. Her sister remained clinically presymptomatic at diagnosis at the age of 28. We concluded that the phenotypic characteristics of WD are possibly attributable to epigenetic/environmental factors.

2024, Journal of biological …

Although there is evidence suggesting a relationship between parkinsonism and modifications to gabaergic, cholinergic and opioid activities in the basal ganglia and related structures, so far studies are not conclusive, and the molecular... more

2024, jbr.gr

Neurochemical changes occurring in the nuclei of the basal ganglia as a consequence of the degeneration of the substantia nigra pars compacta (SNc) that typically occurs in the Parkinson's disease (PD), have been already studied (Zigmond et al., 2002). There are well-established experimental models of parkinsonism using intracerebral injection of 6-hydroxydopamine (6-OHDA) in rodents and systemic or intracarotid delivery of 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in non-human primates that have been instrumental in the investigation of these changes (Blum et al.

2024, Gene Reports

Long non-coding RNAs (lncRNAs) participate in the neurodevelopment and species divergence. They also contribute in the etiology of neuropsychiatric disorders. The highly accelerated region 1a (HAR1A) lncRNA is regarded as one of the features of the evolutionary deviation of humans and chimpanzees and participates in specification and migration of neuron especially in cortex. In the current study, we genotyped a single nucleotide polymorphism (SNP) in this lncRNA (rs750697) in a population of Iranian patients with different neuropsychiatric conditions such as substance addiction, attention deficit hyperactive disorder, bipolar disorder, major depressive disorder and schizophrenia. There was no significant difference between allele and genotype frequencies of this SNP between any subgroup of patients and the corresponding age-and sex-matched controls. Consequently, the current study excludes the participation of the rs750697 SNP in the etiology of neuropsychiatric disorders in Iranian population. Further assessment of other SNPs within this lncRNA might lead to identification of possible risk factors for neuropsychiatric disorders.

2024, Gene Reports

2024, Neuropsychologia

Dopaminergic system of the brain is believed to be strongly involved in normal and pathological behavioral phenotypes of attention. In metacontrast masking studies attentional effects on metacontrast are predominantly expressed when time intervals between a target stimulus and a masking stimulus are longer rather than shorter. Taken together, this predicts that variability in common genes known to be involved in dopaminergic function could interact with target/mask intervals in determining the effects of metacontrast masking. We tested this by genotyping participants of the masking experiment for the COMT Val158Met, DAT1 3'UTR 40bp VNTR, and DRD4 exon 3 48bp VNTR variability. We found that Val homozygotes and subjects with long repeat variants of the DRD4 gene showed relatively higher level of correct target perception with a longer target/mask time interval than with a shorter time interval while DAT1 variability did not have any effects. Implications of this result for the dev...

2024, Neuropsychology Review

2024, The European journal of neuroscience

Dopamine is a potent neuromodulator known to influence glutamatergic transmission in striatal medium spiny neurons (MSNs). It acts on D1 and D2-like dopamine receptors that are expressed on two distinct subpopulations. MSNs projecting to the substantia nigra express D1 receptors (D1Rs) while those projecting to the lateral globus pallidus express D2 receptors (D2Rs). D1R signaling in particular can increase excitatory transmission through varied PKA-dependent, cell-autonomous pathways. Mechanisms by which D1R signaling could increase excitatory transmission in D2R bearing MSNs have been relatively less explored. Herein, we consider the possibility that D1R agonists increase levels of soluble factors that subsequently influence NMDA-stimulated calcium flux in D2R neurons. We focus on matrix metalloproteinases (MMPs) and MMP-generated integrin binding ligands, important soluble effectors of glutamatergic transmission that may be elevated in the setting of excess dopamine. We observe t...