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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevailing neurochemical theory about biological correlates of suicidal behavior focuses on the serotonergic system. In this study, we assessed the cortisol, ACTH, GH, prolactin and temperature responses to flesinoxan, a5-HT1A agonist, in 30 DSM-III-R major depressed inpatients subgrouped into suicide attempters (n = 15) and nonattempters (n = 15). The patients were assessed after a drug-free period of at least 3 weeks. A subsample of 16 patients completed the Buss-Durkee Hostility Inventory as a measure of impulsive aggressive behavior. Mean delta cortisol responses to flesinoxan were significantly lower in the group of depressed patients with a history of suicide attempts than in the group without history of suicidal behavior: for the delta cortisol values 14.5 +/- 16.3 micrograms/l vs 101 +/- 94 micrograms/l (F = 8.9, df = 5.25, p = 0.006). There was also a very significant difference between suicide attempters and nonattempters for the temperature (delta T degrees) responses to flesinoxan: 0.20 +/- 0.24 degrees C vs. 0.60 +/- 0.24 degrees C (F = 18.1, df = 5.25, p = 0.0003). Hormonal and temperature responses to flesinoxan were not correlated with BDHI irritability or assault subscale scores. The results of the present study support the implication of the serotonergic system, particularly 5-HT1A receptors, in the control of self-directed aggressive behavior. Moreover, in depressed patients, serotonergic abnormalities do not appear to be related to aggressive behavior.
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PMID:The flesinoxan 5-HT1A receptor challenge in major depression and suicidal behavior. 861 6

Hormonal responses to challenge with the 5-HT2A/2C probe d-fenfluramine and hormonal and thermal responses to challenge with the 5-HT1A probe ipsapirone were correlated with self-report and historical assessments of aggression in a pilot sample of eight male personality-disordered individuals. Prolactin responses to d-fenfluramine and cortisol responses to ipsapirone challenge were inversely correlated with self-reported assaultiveness. Thermal responses to ipsapirone were inversely correlated with a historical assessment of aggression. Since none of these physiological indices of 5-HT system function were intercorrelated, it is possible that simultaneous assessment of these 5-HT indices may yield a more comprehensive assessment of the relationship between central 5-HT system function and aggressive behavior in humans.
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PMID:Physiological responses to d-fenfluramine and ipsapirone challenge correlate with indices of aggression in males with personality disorder. 867 71

Serotonin metabolism and 5-HT2A and 5-HT1A specific binding were studied in high-aggressive C57BL and low-aggressive CBA mice. In three main tests for anxiety (elevated plus-maze "dark-light test", and social contacts) C57BL mice revealed higher anxiety than CBA, Activity of tryptophan hydroxylase, the key enzyme in serotonin biosynthesis was significantly lower in the midbrain and neostriatum of C57BL than CBA mice. The specific binding of [3H]-ketanserin in C57BL was higher in the frontal cortex and lower in the neostriatum than in the same structures of CBA mice being indicative of the differences in 5-HT2A receptor density. There were no significant differences in 5-HT1A receptor density (as indicated by specific [3H]-8-OH-DPAT binding) between the strains. It was suggested that decreased serotonin metabolism and characteristic distribution of 5-HT2A receptors can underlie the expression of genetic predisposition to anxiety and aggression.
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PMID:[The characteristics of the brain serotonin system and anxiety in the C57BL and CBA mouse strains]. 872 69

Serotonin is a neuromodulator that is involved in a number of mood disorders such as depression, anxiety and impulsive violence. In an attempt to dissect the contribution of individual 5-HT receptor subtypes to behavior, we have generated by homologous recombination, mutant mice lacking the 5-HT1B receptor. These mice did not exhibit any obvious developmental or behavioral defect. However, the hyperlocomotor effect of the 5-HT1A/1B agonist, RU 24969 was completely absent in mutant mice, indicating that this effect is mediated by 5-HT1B receptors. Moreover, when confronted with an intruder, isolated mutant mice attacked the intruder faster and more intensely than wild-type mice, suggesting an involvement of 5-HT1B receptors in the modulation of aggressive behavior. These data might be related to the fact that a class of 5-HT1 agonists, termed serenics, have anti-aggressive properties, and with the findings that certain impulsive aggressive behaviors are associated with deficits in central serotonin.
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PMID:5-HT1B receptor knock out--behavioral consequences. 878 25

The behavioral effects of eltoprazine and haloperidol during a 4 week treatment period were studied in the resident-intruder model of aggression in male rats. Eltoprazine, a serotonergic (5-HT1A/1B) agonist with specific anti-aggressive actions in animals, was compared to haloperidol, a neuroleptic often used to control behavioral disorders. Eltoprazine (1 or 3 mg/kg p.o.) and haloperidol (2 mg/kg p.o.) were given 60 min before a 10 min aggression test. Acutely, eltoprazine reduced aggression, without adversely affecting other behaviors. Eltoprazine (1 or 3 mg/kg p.o.) was subsequently given daily for 4 weeks and aggression tests were performed each week. The anti-aggressive effects of eltoprazine remained stable over the period of 4 weeks whereas exploration was increased. After a wash-out period of 1 week aggression had returned to baseline levels. Acutely given, haloperidol (2 mg/kg p.o.) completely reduced aggression concomitant with massive sedation. Significant tolerance developed to the sedatory actions of haloperidol over the 4 week treatment period. Aggression returned slowly, but remained below baseline values. One week after wash-out a new challenge with haloperidol (2 mg/kg p.o.) revealed significant tolerance. After 2 weeks wash-out aggression had returned to baseline. The data demonstrate persistent and specific anti-aggressive effects after eltoprazine showing no tolerance. In contrast, haloperidol showed tolerance and rebound effects for aggression. The development of tolerance after haloperidol has a different course for sedation than for the anti-aggressive action.
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PMID:Chronic treatment with eltoprazine does not lead to tolerance in its anti-aggressive action, in contrast to haloperidol. 886 31

The purpose of the present paper was to investigate the relationship of the serotonergic and dopaminergic systems to subscales of sensation seeking (SS). Two of the subscales, Disinhibition (DIS) and Experience Seeking (ES), were chosen for analysis based on their representation of the two major factors obtained in a factor analysis: DIS represents a factor of lack of impulse control and ES a factor of novelty seeking. In studies 1 and 2 responsivity to a serotonergic (5-HT) challenge by a 5-HT1a receptor agonist (ipsapirone) was investigated by drug-induced prolactin (PRL) and cortisol responses, as well as by emotional states and behavioral measures. The dopaminergic (DA) response to a DA agonist (lisuride) and antagonist (fluphenazine) was analyzed in a condition of smoking deprivation (study 3) using PRL responses, emotional states, and behavioral measures of nicotine craving as dependent variables. In the studies of the serotonergic system, high ES subjects showed a blunted cortisol response in both studies and high DIS subjects demonstrated a blunted PRL response in study 2. A frequently observed side effect of serotonergic agonists, increase in emotional arousal, was not observable with ipsapirone in high ES and high DIS subjects as compared to low scorers. Behavioral aggression, which had been experimentally induced in study 2, was increased in high ES as well as in high DIS by the 5-HT1a agonist which exerted antiaggressive effects in low scorers. These findings were found compatible with the idea of a generally low responsivity of the serotonergic system in high ES as well as in high DIS types of sensation seekers of 5-HT1a subsensitivity in high DIS and subsensitivity of other postsynaptic 5-HT receptors in high ES. There was no association between SS subscales and DA-induced decrease of PRL, but high ES subjects seemed to tolerate nicotine deprivation better than low ES subjects indicating that they were less susceptible to deprivation of nicotine-induced DA. But craving for nicotine was increased in high ES subjects by the DA agonist lisuride as opposed to the antagonist, which was taken as evidence that DA stimulation may induce approach behavior in high ES. Although only two subscales had been selected for the investigation, this approach suggests both common and different relationships between SS subscales and neurotransmitter systems.
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PMID:Serotonin and dopamine as mediators of sensation seeking behavior. 891 73

The brain 5-HT1A receptor system in male wild house mice selected for high and low offensive aggression was investigated by autoradiographic analysis of in situ hybridization and radioligand binding. In high-aggressive mice, characterized by a short attack latency, the rise in plasma corticosterone concentration during the early dark phase was reduced. At that time the level of 5-HT1A mRNA in the dorsal hippocampus (dentate gyrus and CA1) was twice the amount measured in low-aggressive mice that had long attack latency and high plasma corticosterone level. Increased postsynaptic 5-HT1A receptor radioligand binding was found in dentate gyrus, CA1, lateral septum, and frontal cortex. No difference in ligand binding was found for the 5-HT1A autoreceptor on cell bodies in the dorsal raphe nucleus. In conclusion, genetic selection for high offensive aggression co-selects for reduced (circadian peak) level in plasma corticosterone and increased postsynaptic 5-HT1A receptor number in limbic and cortical regions.
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PMID:Enhanced 5-HT1A receptor expression in forebrain regions of aggressive house mice. 893 Mar 40

The hypothesis is proposed of a new subtype of depression named: stressor-precipitated, cortisol-induced, serotonin-related, anxiety/aggression-driven depression (SeCA depression). Biologically, these patients are characterized by impaired 5-HT synthesis and reduced 5-HT1A receptor sensitivity. Under normal conditions these functions proceed marginally; in times of stress they easily fail, due to sustained overproduction of cortisol. Psychopathologically this depression type shows the following characteristics: anxiety and aggression, not mood lowering, heralding a depressive episode; the personality structure shows 'character neurotic' impairments and tolerance for (certain) traumatic life events is low. As specific therapeutic agents selective 5-HT1A agonists and cortisol or CRH antagonists are proposed. Prophylactically, maintenance treatment with 5-HT1A agonists seems indicated as well as psychological interventions to increase the stressor threshold.
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PMID:Faulty cortisol/serotonin interplay. Psychopathological and biological characterisation of a new, hypothetical depression subtype (SeCA depression) 970 3

The behavioral profiles of five clinically used selective serotonin reuptake inhibitors (SSRIs) citalopram, paroxetine, sertraline, fluvoxamine and fluoxetine, have been compared in animal models of antidepressant (mouse forced swim test), anxiolytic (exploration of black and white test box and foot-shock-induced ultrasonic vocalization in the rat) and antiaggressive (isolation-induced aggressive behavior in the mouse) activity. the results are discussed in relation to receptor binding data from the literature. Furthermore, affinities for the sigma 1 and sigma 2 binding sites are presented. Citalopram reversed the immobility induced by forced swimming with a potency similar to that of imipramine. Paroxetine, fluvoxamine and fluoxetine reversed swim-induced immobility less potently and with a maximum of 40-50% reversal. Citalopram produced a mixed anxiogenic-/anxiolytic-like response in rats tested in the two-compartment black and white box. Paroxetine induced an anxiogenic-like response at low doses and the other SSRIs were without major effects. Citalopram and paroxetine inhibited footshock-induced ultrasonic vocalization with high potencies. The dose-response curve was biphasic for citalopram with a maximum of 64% inhibition. Sertraline and fluvoxamine inhibited the vocalization less potently, and fluoxetine induced a weak inhibitory effect corresponding to a maximum of 32%. Sertraline, fluvoxamine and fluoxetine inhibited isolation-induced aggressive behavior, whereas citalopram and paroxetine were inactive. Both 5-HT1 and 5-HT2 receptors are involved, and there was a functional interaction between 5-HT1A and 5-HT2A or 5-HT2C receptors, as ritanserin potentiated the antiaggressive effect of 1,5-HTP as well as that of 8-OH-DPAT.
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PMID:Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike? 908 57

As noted previously, it is likely that the tendency to lash out verbally or physically at others is influenced by an interaction among multiple complex biologic factors. We need to investigate how these systems interact with each other to develop a more thorough understanding of the brain's influence over aggressive behavior. We are at a very early stage in our understanding of the neurobiology of aggression. There are no simple tools for studying the complex neurophysiology of the human brain. The studies cited in this article include techniques limited in their utility. As our technologies improve, discovering a more thorough picture of the brain's influence over aggressive behavior may be possible. For example, functional neuroimaging may help to localize abnormal neurotransmitter functioning in the brains of individuals with impulsive aggressive behavior. Our technologies are beginning to reveal the differential effects of subsystems of neurotransmitter regulation. Subtypes of serotonin receptors may differentially mediate impulsive aggressive behaviors. Animal studies suggest that 5-HT 1A receptor stimulation results in a decrease in aggressive behavior. As noted previously, aggressive personality-disordered patients show a blunted prolactin response to the 5-HT1A agonist buspirone. Antagonism of 5-HT 2 receptors appears to decrease aggression, and this effect may explain the ability of newer antipsychotic agents (which, unlike older antipsychotic medications, block 5-HT 2 receptors) to produce a dramatic reduction in aggression and agitation independent of effects on psychotic symptoms. Neglecting psychosocial factors in the causes of aggressive behavior would also be naive. Although environmental factors account for much of the predisposition to aggression, there have been few systematic studies to explore the relationship between life experiences and aggression. In addition, there have been no well-designed studies of the interaction between biology and an individual's environment in the genesis of aggressive behavior. There is some evidence of an association between childhood abuse and neglect and adult antisocial personality disorder, but this relationship might be merely an artifact of the genetic relationship between parental and offspring antisocial personality disorder. As we discussed in the introduction, one of the biggest hurdles in the study of the neurobiology of aggression is the lack of a consensus on definitions. "Intermittent Explosive Disorder" is the only category in DSM-IV that directly addresses individuals with problems with aggression, but the criteria are vague and only focus on a handful of the many patients who exhibit problems with aggressive behavior. It is our hope that investigators in this field can work together toward developing more precise and encompassing diagnostic criteria to study effectively both the neurobiology and treatment of these disorders.
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PMID:The neurobiology of impulsive aggression. 919 21


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