Social Impulsivity Inversely Associated with CSF 5-HIAA and Fluoxetine Exposure in Vervet Monkeys (original) (raw)
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The Role of Serotonin in Aggression and Impulsiveness
Serotonin - A Chemical Messenger Between All Types of Living Cells, 2017
Serotonin is a neuromodulator that has a critical role on the regulation of essential events in neuronal and glial development, such as cell proliferation, differentiation, migration, apoptosis, and synaptogenesis, and acts as a developmental signal. It has been known that a serotonergic system is associated with many psychiatric disorders. The serotonergic system also predominates on the etiopathogenesis of two important endophenotypes: impulsivity and aggression. Impulsiveness is defined as personality trait and an implusive temperament is associated with clinical conditions such as pathological gambling, eating disorders, and borderline personality disorder as well as being a risk factor for self-harm, suicide, and emotional liability. Aggression is not a personality trait like impulsivity, but it is the behavior of harm or injury to others. Besides being a natural human behavior toward survival, aggression can be harmful to the individual and the community when it is constant and excessive. In this chapter, we aimed to review the role of the serotonergic system on impulsivity and aggression, which are two important endophenotypes that identified in many psychiatric disorders.
Aggression and brain serotonergic responsivity: Response to slides in male macaques
Physiology & Behavior, 1995
Aggression and brain serotonergic responsivity: Response to slides in male macaques. PHYSIOL BEHAV 57(2) 205-208, 1995.--The association between central serotonergic responsivity (measured by prolactin response to acute administration of fenfluramine hydrochloride) and aggressivity was examined in 40 adult male cynomolgus monkeys (Macaca fascicularis). Prolactin response to fenfluramine was distributed bimodally with 24 monkeys displaying a "low" prolactin response and 15 showing a "high" prolactin response to the fenfluramine challenge. Behavioral responsivity was assessed by placing the monkeys individually in an open-field enclosure and presenting a series of photographic slides depicting both threatening and nonthreatening images. Monkeys that were low prolactin responders displayed significantly more aggressive gestures in response to a threatening slide of a human being than did the high responders (p < 0.05). Insofar as fenfluramine-stimulated prolactin release assesses serotonergic responsivity, these data support related findings in people and nonhuman primates linking reduced serotonergic activity and aggression.
A synergic effect between lowered serotonin and novel situations on impulsivity measured by CPT
Journal of Clinical and Experimental Neuropsychology, 2008
Rapid tryptophan depletion studies investigate serotonin using amino acid precursor depletion, which transiently reduces the brain level of serotonin. This study compares the effects of serotonin reduction given on the first test day (when the situation is novel) with the effects of serotonin reduction given on the second test day (when the environment and test battery are familiar). A total of 24 healthy young males were given either active tryptophan depletion or placebo in this randomized cross-over design, while impulsivity was measured by a continuous performance test. The participants showed more impulsive responses and reduced attention during tryptophan depletion, but only when this was given on the first test day when the task was novel. This could be caused by a synergic effect between novel situations and reduced neurotransmission of serotonin.
The neuropharmacology of impulsive behaviour
Trends in Pharmacological Sciences, 2008
Impulsivity is a heterogenous phenomenon encompassing several behavioural phenomena that can be dissociated neuroanatomically as well as pharmacologically. Impulsivity is pathological in several psychiatric disorders including attentiondeficit/hyperactivity disorder (ADHD), drug addiction and personality disorders. Pharmacological agents alleviating impulsivity therefore might substantially aid the treatment of these disorders. The availability of preclinical models that measure various forms of impulsivity has greatly increased our understanding of its neuropharmacological substrates. Historically, deficits in central serotonin neurotransmission are thought to underlie impulsivity. Accumulating evidence also points towards an important role of brain dopamine and noradrenaline systems in impulsive behaviour, consistent with the therapeutic efficacy of amphetamine, methylphenidate and atomoxetine in ADHD. However, recent findings also implicate glutamate and cannabinoid neurotransmission in impulsivity. In this review, we will discuss some of the recent developments in the neuropharmacological manipulation of impulsive behaviour.
Neuropsychopharmacology, 2010
The selective breeding of Roman high-(RHA) and low-avoidance (RLA) rats for rapid vs extremely poor acquisition of active avoidance behavior in a shuttle-box has generated two phenotypes with different emotional and motivational profiles. The phenotypic traits of the Roman rat lines/strains (outbred or inbred, respectively) include differences in sensation/novelty seeking, anxiety/fearfulness, stress responsivity, and susceptibility to addictive substances. We designed the present study to characterize differences between the inbred RHA-I and RLA-I strains in the impulsivity trait by evaluating different aspects of the multifaceted nature of impulsive behaviors using two different models of impulsivity, the delay-discounting task and five-choice serial reaction time (5-CSRT) task. Previously, rats were evaluated on a scheduleinduced polydipsia (SIP) task that has been proposed as a model of obsessive-compulsive disorder. RHA-I rats showed an increased acquisition of the SIP task, higher choice impulsivity in the delay-discounting task, and poor inhibitory control as shown by increased premature responses in the 5-CSRT task. Therefore, RHA-I rats manifested an increased impulsivity phenotype compared to RLA-I rats. Moreover, these differences in impulsivity were associated with basal neurochemical differences in striatum and nucleus accumbens monoamines found between the two strains. These findings characterize the Roman rat strains as a valid model for studying the different aspects of impulsive behavior and for investigating the mechanisms involved in individual predisposition to impulsivity and its related psychopathologies. Fernández-Teruel A, Tobeña A (2003).Fearfulness and sex in F2 Roman rats: males display more fear though both sexes share the same fearfulness traits. Physiol Behav 78:723-732. American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders (4 th edn) text revision. American Psychiatric Press: Washington, DC. Anderson KG, Woolverton WL (2005). Effects of clomipramine on self-control choice in Lewis and Fischer 344 rats. Pharmacol Biochem Behav 80: 387-393. Annetrude JG, de Mooij-van Malsen A, Berend Olivier AB, Martien JHKas. (2008). Behavioural genetics in mood and anxiety: A next step in finding novel pharmacological targets. Eur J Pharmacol 585: 436-440. Aubry JM, Bartanusz V, Driscoll P, Schulz P, Steimer T, Kiss Jz (1995). Corticotropin-releasing factor and vasopressin mRNA levels in Roman high-and low-avoidance rats: response to openfield exposure. Neuroendocrinology 61: 89-97. Broadhurst PL, Bignami G (1965). Correlative effects of psychogenetic selection: a study of the Roman high and low avoidance strains of rats. Behav Res Ther 3: 273-280. (2006). Vulnerability of long-term neurotoxicity of chlorpyrifos: effect on schedule-induced polydipsia and a delay discounting task. Psychopharmacology 189(1): 47-57. Carli M, Robbins TW, Evenden JL, Everitt BJ (1983). Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9: 361-380. Carrasco J, Márquez C, Nadal R, Tobeña A, Fernández-Teruel A, Armario A (2008). Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strains. Psychoneuroendocrinology 33:437-445. Chakroun N, Doron J, Swendsen J (2004). Substance use, affective problems and personality traits: test of two association models. Encephale 30(6): 564-569. Charnay Y, Steimer T, Huguenin C, Driscoll P (1995). [ 3 H] Paroxetine binding sites: brain regional differences between two psychogenetically selected lines of rats. Neurosci Res Comm. 16: 29-35. O (2005). The psychogenetically selected Roman rat lines differ in the susceptibility to develop amphetamine sensitization. Behav Brain Res 157(1):147-156. Crabbe JC (2002). Genetic contributions to addiction. Annu Rev Psychol 53:435-62. Dalley JW, Mar AC, Economidou D, Robbins TW (2008). Neurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90(2): 250-60. Dalley JW, Theobald DE, Pereira EA, Li PM, Robbins TW (2002). Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity.Psychopharmacology 164(3):329-40. Daruna JH, Barnes PA (1993). A neurodevelopmental view of impulsivity. In: McCown WG, Johnson JL, Shure MB (eds). The impulsive client: Theory, research and treatment. Washington DC: American Psychological Association, pp 23-37.
Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals
Psychopharmacology, 2002
Rationale: Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce. Objectives: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. Methods: Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. Results: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan/large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive-or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. Conclusions: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.
Serotonin, emotions and the social brain
Nevropsykologi, 2011
Multiple lines of evidence from animal and human research relate the neurotransmitter serotonin to aspects of emotions, personality and social behaviour, and this neurotransmitter system is targeted in drug treatment of mood and anxiety disorders. A major research program in Copenhagen (Cimbi) focuses on the neural bases-serotonin in particular-of personality dimensions that predispose individuals to affective and substance use disorders. This symposium dealt with highlights from both this research program and from a large SSri treatment study, and preliminary analyses of social cognitive measures from both of these research programs were included as well. Projections from the raphe nuclei in the brainstem (figure 1) reach most of the brain, where serotonin acts to modulate neural processing. it is an exceedingly complex system, as there are more than a dozen subtypes of serotonin receptors, which seem to have separate functions. early indicators of its role in social functions include studies in the vervet monkey (raleigh et al., 1991, 1996). Treatment with enhancement or conversely reduction of serotonergic activity determined social status (when it was uncertain with the dominant male removed), and in this situation eventual acquisition of dominance was preceded by an early increase in prosocial behaviour. observational studies indicated that prosocial behaviours are related to high 5-HT2A receptor density in orbitofrontal and medial prefrontal cortex, and in amygdala. These and related results from humans (e.g. Knutson et al., 1998) form part of the basis for current research and hypotheses (Gade).
Psychopharmacology, 2004
Rationale: Global serotonin (5-HT) depletion increases the number of premature responses made on the five-choice serial reaction time task (5CSRT) in rats. In contrast, the 5-HT 2A receptor antagonist M100907 decreases this measure of impulsivity. Mounting evidence suggests that 5-HT 2A and 5-HT 2C receptors have opposing effects on behaviour, and that the 5-HT 2C receptor antagonist SB 242084 produces a pattern of behaviour similar to 5-HT depletion. Objectives: To assess the effects of 5-HT 2A and 5-HT 2C receptor antagonists on performance of the 5CSRT, to directly compare the effects of these drugs with those of ICV 5,7-dihydroxytryptamine (5,7-DHT) lesions and to investigate whether 5-HT depletion affects the action of these agents. Methods: The effects of M100907 (0, 0.01, 0.03, 0.1 mg/kg IP) and SB 242084 (0, 0.1, 0.25, 0.5 mg/kg IP) were investigated on performance of the 5CSRT in both ICV 5,7-DHTlesioned and sham-operated rats. Results: ICV 5,7-DHT lesions, which significantly decreased forebrain levels of 5-HT by around 90%, increased levels of premature responding, decreased omissions and the latency to respond correctly, yet did not affect performance accuracy. M100907 decreased premature responding in shamoperated controls but not in 5-HT-depleted rats. In contrast, SB 242084 increased premature responding in all animals, and also decreased the latency to make a correct response in sham-operated controls. Conclusions: These data support the view that serotoner-gic regulation of impulsive behaviour through different members of the 5-HT 2 receptor family is functionally heterogeneous. Although both 5-HT 2A and 5-HT 2C receptors participate in controlling this form of impulsive action, their relative contribution may depend on the endogenous state of the 5-HT system.
Gade2011 serotonin emotions the social brain
Nevropsykologi, 2011
Multiple lines of evidence from animal and human research relate the neurotransmitter serotonin to aspects of emotions, personality and social behaviour, and this neurotransmitter system is targeted in drug treatment of mood and anxiety disorders. A major research program in Copenhagen (Cimbi) focuses on the neural bases-serotonin in particular-of personality dimensions that predispose individuals to affective and substance use disorders. This symposium dealt with highlights from both this research program and from a large SSri treatment study, and preliminary analyses of social cognitive measures from both of these research programs were included as well. Projections from the raphe nuclei in the brainstem (figure 1) reach most of the brain, where serotonin acts to modulate neural processing. it is an exceedingly complex system, as there are more than a dozen subtypes of serotonin receptors, which seem to have separate functions. early indicators of its role in social functions include studies in the vervet monkey (raleigh et al., 1991, 1996). Treatment with enhancement or conversely reduction of serotonergic activity determined social status (when it was uncertain with the dominant male removed), and in this situation eventual acquisition of dominance was preceded by an early increase in prosocial behaviour. observational studies indicated that prosocial behaviours are related to high 5-HT2A receptor density in orbitofrontal and medial prefrontal cortex, and in amygdala. These and related results from humans (e.g. Knutson et al., 1998) form part of the basis for current research and hypotheses (Gade).