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Neurobiological processes underlying the epidemiologically established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals who are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. [ABSTRACT FROM AUTHOR]

Rationale: Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. Objective: We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regulation and modulation by other amines, acids and peptides. Results: New pharmacological tools differentiate the first three 5-HT receptor families and their modulation by GABA, glutamate and CRF. Activation of 5-HT, 5-HT and 5-HT receptors in mesocorticolimbic areas, reduce species-typical and other aggressive behaviors. In contrast, agonists at 5-HT and 5-HT receptors in the medial prefrontal cortex or septal area can increase aggressive behavior under specific conditions. Activation of serotonin transporters reduce mainly pathological aggression. Genetic analyses of aggressive individuals have identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT, 5-HT transporter, Pet1, MAOA) or indirectly (e.g., Neuropeptide Y, αCaMKII, NOS, BDNF). Dysfunction in genes for MAOA escalates pathological aggression in rodents and humans, particularly in interaction with specific experiences. Conclusions: Feedback to autoreceptors of the 5-HT family and modulation via heteroreceptors are important in the expression of aggressive behavior. Tonic increase of the 5-HT family expression may cause escalated aggression, whereas the phasic increase of 5-HT receptors inhibits aggressive behaviors. Polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT modulate aggression, often requiring interaction with the rearing environment. [ABSTRACT FROM AUTHOR]

The present review focuses on what is known of basic serotonin physiology in the human body. Here, we describe serotonin biochemistry and metabolism and summarize the results of studies that have contributed significantly to our understanding of serotonin physiology. We report the well-established role of serotonin in cardiovascular, gastrointestinal, and circulatory physiology. Emphasis is placed on the role of serotonin in peripheral physiological systems rather than in the central nervous system. A brief overview is provided on the emerging role of serotonin in novel areas such as bone pathways and glucose uptake. We also report a select few animal studies and animal models that have provided worthwhile contributions to the understanding of serotonin in human physiology. In addition, we summarize the results of large-scale genetic studies on serotonin and serotonin transporter genes, performed in relation to behavioral and mood disorders. J. Cell. Physiol. 217: 301–306, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The neurotransmitter serotonin (5-HT) has been implicated in the modulation of aggression in animals and humans. A longstanding dogma that aggression and serotonergic activity are inversely related has to be abandoned in light of many new findings. Trait and state aggression are differentially regulated by the 5-HT system and different 5-HT receptors seem to be involved. Of the 14 different 5-HT receptors, the 5-HT1B receptor, particularly the postsynaptically located 5-HT1B heteroreceptor, plays a highly selective role in the modulation of offensive aggression. We are still far from understanding the complex role played by the serotonergic system in the modulation of a complex set of behaviors like aggression. [ABSTRACT FROM AUTHOR]

Experiments with social instigation or the omission of scheduled reinforcement show that serotonergic mechanisms may be involved in escalated aggression in animals. 5-HT1B receptor agonists have anti-aggressive effects in individuals who show moderate as well as high levels of aggression. The present study compared the effects of the 5-HT1B agonist anpirtoline (0.125–1.5 mg/kg) on (1) species-typical aggressive behavior in male mice, (2) aggression “instigated” or primed by prior exposure to the opponent, and (3) aggression heightened by “frustration” caused by omission of scheduled reinforcement. The effects of anpirtoline on species-typical behavior were also assessed after pretreatment with the 5-HT1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline, like other 5-HT1B agonists (CP-94,253, zolmitriptan), decreased both instigated and frustration-heightened aggression, while motor behavior was unaffected. The aggression-inhibiting effects of anpirtoline were blocked by pretreatment with GR127935. The current results indicate that the 5-HT1B receptor is critically involved in the modulation of escalated aggression. [Copyright &y& Elsevier]

Quipazine, a serotonin receptor stimulant, inhibited the response of rats to painful stimuli in two methods currently used to measure antinociception in these animals: the hot plate and tail compression test. The antinociceptive action was observed with doses ranging from 5 to 20 mg/kg i.p. according to the test situation. The effect was significantly antagonized by a pretreatment with methergoline, a potent serotonin antagonist. An electrolytic lesion placed in the nucleus raphe medianus, which produced a marked decrease of serotonin in the forebrain did not, or only slightly, affected the effect of quipazine, depending on the method used to measure antinociception. It is suggested that quipazine can produce antinociceptive action in rats by interacting with a serotonergic mechanism. The action appears to be due mainly to a direct action on postsynaptic serotonin receptors, although a presynaptic component can also contribute to the effect of quipazine. [ABSTRACT FROM AUTHOR]

Sensitive radioisotopic enzymatic methods were used to determine 5-HT levels in 16 different regions of brain from rats anesthetized for 90-105 min with 1% halothane or 18% cyclopropane. These two anesthetics were chosen because of their differing effects on the electroencephalogram and on the cardio-vascular and respiratory systems. 5-HT levels in the nucleus amygdaloideus centralis, substantia nigra, and nucleus centralis superior were increased after administration of either anesthetic, but only anesthesia with cyclopropane was associated with an increase in 5-HT level in the nucleus raphe dorsalis. The changes in levels of transmitter does not distinguish cause from effect of anesthesia, and further experiments are needed to delineate what role, if any, the specific areas play in muscle relaxation, analgesia, sleep or anesthesia. [ABSTRACT FROM AUTHOR]

The effects of Para-chlorophenylalanine (P-CPA) on the discrimination of a low intensity tone were evaluated. Three rats were trained in a two-lever operant chamber to press the right lever to terminate a tone and to press the left lever when the tone was off for food reinforcement. Errors, consisting of left-lever responses when the tone was on or right-lever responses when the tone was off, were recorded and used to determine the percent of the total responses that were correct. After training to essentially errorless performance, the tone intensity was lowered until the rats were performing at about 75% correct responses. After each rat achieved a stability criterion, it was treated P. O. with 150 mg/kg of P-CPA in mineral oil or with mineral oil alone. Each rat received P-CPA at least twice and mineral oil alone at least once. P-CPA consistently elevated the percent of correct responses while depressing the over-all response rate. Mineral oil had no effect on either measure. [ABSTRACT FROM AUTHOR]

Two different techniques were employed to measure morphine analgesia, the hot-plate and the tail compression. An intraventricular injection of 6-hydroxydopamine, which produced a marked decrease of brain noradrenaline and dopamine, strongly potentiated the analgesic effect of morphine. The lesion of midbrain raphe, which lowers forebrain serotonin, antagonized morphine analgesia. 5-Hydroxytryptophan restored serotonin levels and the analgesic effect of morphine in midbrain raphe lesioned rats. The role of brain serotonin and catecholamines on morphine analgesia is discussed. [ABSTRACT FROM AUTHOR]

Primates must balance the need to monitor other conspecifics to gain social information while not losing other resource opportunities. We consolidate evidence across the fields of primatology, psychology, and neuroscience to examine individual, population, and species differences in how primates, particularly macaques, monitor conspecifics. We particularly consider the role of serotonin in mediating social competency via social attention, aggression, and dominance behaviors. Finally, we consider how the evolution of variation in social tolerance, aggression, and social monitoring might be explained by differences in serotonergic function in macaques. This article is categorized under:Economics > Interactive Decision‐MakingPsychology > Comparative PsychologyNeuroscience > BehaviorCognitive Biology > Evolutionary Roots of Cognition [ABSTRACT FROM AUTHOR]

Abstract Autonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before an aggressive confrontation that was omitted at the regular time of occurrence, dissociating the motoric from the aminergic activity. Dopamine, serotonin, heart rate and behavioral activity were monitored before, during and after a single 10-min confrontation in resident male Long-Evans rats fitted with a microdialysis probe in the n. accumbens and with a telemetry sender (experiment 1). DA, but not 5-HT efflux, was confirmed to increase in n. accumbens during and after a single aggressive episode. In aggressive males that confronted an opponent daily for 10 days (experiment 2) heart rate rose 1 h before the regularly scheduled encounter relative to control rats, as measured on day 11 in the absence of any aggression. Concurrently, DA levels increased by 60–70% over baseline levels and 5-HT levels decreased by 30–35% compared to baseline levels. These changes were sustained over 1 h, and contrasted with no significant changes in DA, 5-HT, heart rate or behavioral activity in control rats. The rise in mesolimbic DA appears to be significant in anticipating the physiological and behavioral demands of an aggressive episode, and the fall in 5-HT in its termination, dissociated from the actual execution of the behavior. [ABSTRACT FROM AUTHOR]