Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggressive behaviour exhibited by domestic pigs following encounters with unfamiliar individuals is a serious welfare and economical problem. Aggression resulting in skin lesions is similarly prevalent in prepubertal pigs of either sex. Little is known about the neural circuits and neuropeptides that control aggression in the pig. Because there is evidence for the involvement of the vasopressin and serotonergic systems in the regulation of aggressive behaviour in male mammals, we sought differences using quantitative in situ hybridisation of vasopressin and serotonin 1A receptor (5-HT1A) mRNA expression within specific brain regions of aggressive and nonaggressive prepubertal female pigs. The number of cells expressing vasopressin mRNA was significantly higher in aggressive pigs in the medial amygdala, lateral septum (LS) and showed a similar trend in the bed nucleus of the stria terminalis (BnST) but not the paraventricular nucleus (PVN) or supraoptic nucleus. The 5-HT1A receptor was widely expressed through the porcine brain and a significantly lower intensity (silver grain density) of 5-HT1A mRNA expression was observed in the BnST. In the medial amygdala and LS fewer cells expressed 5-HT1A mRNA in aggressive pigs but no differences were found in the PVN. In the absence of inbred strains or selection lines, these findings have shown that prior identification of phenotypic behavioural extremes in a population in advance of neural studies is a useful technique. Moreover, these findings support a central role for vasopressin and serotonin in the mediation of high trait aggression in prepubertal female pigs.
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PMID:Resident-intruder trait aggression is associated with differences in lysine vasopressin and serotonin receptor 1A (5-HT1A) mRNA expression in the brain of pre-pubertal female domestic pigs (Sus scrofa). 1615 81

Variation in genes coding for proteins that control serotonin (5-HT) system development, plasticity and function have been implicated in various aspects of complex behaviour including anxiety and aggression. Based on the remarkable progress in technologies that allow the alteration or elimination of individual genes to create transgenic animal models, gene knockout strategies further increase our knowledge about which serotonergic gene products are involved in behavioural traits. This overview selects anxiety and aggression as paradigmatic traits and behaviours, and focuses on mouse models which have been modified by deletion of genes coding for key players of serotonergic neurotransmission. In particular, phenotypic changes in mice bearing inactivation mutations of 5-HT1A and 5-HT1B receptors, 5-HT transporter, 5-HT neuron-specific transcription factor Pet1, monoamine oxidase A and genes related to 5-HT signalling will be discussed and major findings highlighted. However, because a missing gene might affect many developmental processes throughout ontogeny and compensatory mechanisms may be activated in knockouts, behavioural data from mice with targeted gene deletions should be interpreted with caution. The development of conditional knockout mice, in which a specific gene can be inactivated neurocircuit-specifically at any time, is therefore likely to avert the deficiencies associated with behavioural data from classical constitutive knockouts.
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PMID:Serotonergic gene inactivation in mice: models for anxiety and aggression? 1620 78

The serotonergic system in the CNS has complex interactions with many, if not all other neurotransmitter systems in the brain. Its localization, distribution and amazing receptor diversity makes it an appealing system for modulatory aspects in many basic behaviours, including food and water intake, sexual behaviour and aggression. Notwithstanding decades of research into the putative role of the serotonergic system in aggression, no clear picture about its specific role has emerged. It seems, dependent on state or trait, to be involved in either the performance or the termination of aggressive behaviours. The present technology appears not developed enough to give answers to these questions. Application of drugs and particular selective ligands for certain subtype receptors seems a more promising approach to unravelling the role of 5-HT in aggression. The (postsynaptic) 5-HT1B and to a lesser extent, the 5-HT1A receptor seems to play a prominent role, at least in rodents, in the modulation of (offensive) aggression.
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PMID:Serotonergic mechanisms in aggression. 1620 80

Aggressive behavior is the most frequently encountered behavioral problem in dogs. Abnormalities in brain serotonin metabolism have been described in aggressive dogs. We studied canine serotonergic genes to investigate genetic factors underlying canine aggression. Here, we describe the characterization of three genes of the canine serotonergic system: the serotonin receptor 1A and 2A gene (htr1A and htr2A) and the serotonin transporter gene (slc6A4). We isolated canine bacterial artificial chromosome clones containing these genes and designed oligonucleotides for genomic sequencing of coding regions and intron-exon boundaries. Golden retrievers were analyzed for DNA sequence variations. We found two nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of htr1A; one SNP close to a splice site in htr2A; and two SNPs in slc6A4, one in the coding sequence and one close to a splice site. In addition, we identified a polymorphic microsatellite marker for each gene. Htr1A is a strong candidate for involvement in the domestication of the dog. We genotyped the htr1A SNPs in 41 dogs of seven breeds with diverse behavioral characteristics. At least three SNP haplotypes were found. Our results do not support involvement of the gene in domestication.
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PMID:Structure and variation of three canine genes involved in serotonin binding and transport: the serotonin receptor 1A gene (htr1A), serotonin receptor 2A gene (htr2A), and serotonin transporter gene (slc6A4). 1625 23

Knowledge about individual differences in behavioural traits and their neurostructural and neurochemical correlates should improve therapeutic approaches of corresponding psychopathology. The presented investigations are aimed to reveal interrelationships between central nervous serotonergic [5-HT] receptor densities and neurochemical as well as behavioural traits in two mice strains. Male AB-Halle [ABH] and AB-Gatersleben [ABG] mice differing in aggression were investigated after 6 weeks of isolation housing. 5-HT1A and 5-HT2A receptors were analysed in different brain regions by in vitro autoradiography. HPLC determinations of aminergic transmission in the cortex, hippocampus, striatum as well as in the raphe-region and radioimmunoassay determination of serum corticosterone were done before (basal condition) and after behavioural tests (challenge condition). Receptor autoradiography revealed higher 5-HT1A receptor densities, especially in limbic regions, and lower 5-HT2A receptor densities in the basal ganglia of ABH mice. Furthermore, ABH mice characterized as behaviourally more active in the open field and plus maze as well as more reactive and aggressive during the social interaction test showed lower basal 5-hydroxyindolacetic acid [5-HIAA] concentrations in the hippocampus, cortex and raphe-region as well as a different activation pattern in serotonergic, dopaminergic and noradrenergic brain systems after challenge in comparison to ABG mice. Additionally lower corticosterone concentrations were found in ABH mice. Lower basal serotonergic and striatal dopaminergic, but higher basal cortical dopaminergic metabolism in contrast to enhanced challenge-induced central nervous serotonergic and cortical dopaminergic reactivities are discussed to be crucial for an enhanced reactive behavioural trait, which could secondarily result in aggression-related behaviours, where higher 5-HT1A receptor and lower 5-HT2A receptor densities may be essential.
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PMID:Serotonin 1A and 2A receptor densities, neurochemical and behavioural characteristics in two closely related mice strains after long-term isolation. 1641 47

Serotonergic (5-HT) receptors are crucial for different brain functions and play an important role in several pathological conditions. We analysed [3H]8-OH-DPAT-specific binding to 5-HT1A receptors in male and female mice after group or isolation housing by in vitro autoradiography (n = 6 per group). Females displayed higher postsynaptic 5-HT1A receptor binding compared to males, especially in the cortex. In contrast, lower [3H]8-OH-DPAT-specific binding was found in the female hippocampus. No sex difference was seen for the somatodendritic 5-HT1A autoreceptor. Sex differences in postsynaptic 5-HT1A receptor binding should be relevant to behavioural sex differences, especially in locomotor activity and hippocampus-dependent behaviours. Six weeks isolation housing caused an increase in 5-HT1A receptor binding in most of the brain regions analysed and was more pronounced in males. In isolated males, the increases were detected in the CA1 field of the hippocampus (+16.8%), in the septum (+76.8%), in the cortical amygdala (+24.6%), in the periaqueductal gray (+67.2%) and in the different cortical regions analysed (+61.8-81.4%). [3H]8-OH-DPAT-specific binding increased significantly in the dentate gyrus (+47.1%), the supramammillary nucleus (+31.2%) and in the ventromedial hypothalamus (+34.4%) of isolated females. Sex-dependent isolation-induced alterations in [3H]8-OH-DPAT-specific binding were also found in the raphe nuclei. Isolation-induced increases in 5-HT1A receptor binding could be relevant to the behavioural disinhibition with heightened arousal, impulsivity and activity often observed in isolates. The male-specific alterations in the corticolimbic system as well as in the midbrain could be crucial for isolation-induced aggression.
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PMID:The influence of sex and social isolation housing on pre- and postsynaptic 5-HT1A receptors. 1681 51

A number of molecular genetic studies have investigated if serotonin (5-HT) receptor subtypes are involved in the pathogenesis of depression, suicidal behavior, aggression, and impulsive behavior. Existence of many receptor subtypes for a single transmitter permits a great diversity of signaling raising the possibility that they may serve as genetic markers for suicidal behavior. Most previous studies of suicide have analyzed polymorphisms of the receptors 5-HT1A, 5-HT1B, 5-HT2A, fewer have examined 5-HT1F. We report a study of possible association between the polymorphisms in the 5-HT receptor genes (1A, 1B, 1F, and 2A) and suicidal behavior on a sample of 226 suicide victims and 225 healthy control subjects. No significant differences in genotype frequency distributions between the suicide victims and healthy control subjects were observed for four polymorphisms; three were not polymorphic. A single polymorphism, C-1420T in gene 5-HT2A, showed a slight association with suicide (chi2= 4.94, df = 2, P = 0.067), but the correlation was not statistically significant. None of the tested genetic variants of serotonin receptors appears to be associated with suicidal behavior in the Slovenian population which has a relatively high suicide rate.
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PMID:Association study of seven polymorphisms in four serotonin receptor genes on suicide victims. 1685 20

Mice of two strains with different levels of male aggression (RSB and RLB) were subjected to daily injections of 5-HT1A receptor agonist buspirone (25 microg) on the 2nd - 6th postnatal days. This neonatal treatment augmented the aggressive behavior (tested in the dyadic contests with non-aggressive A/Sn males) in aggressive RSB mice and reduced aggression in less aggressive RLB. Correlations with different signs were found between the 5-HT and 5-HIAA levels in the neocortex, hippocampus, and hypothalamus and behavioral indices of aggression in RSB and RLB males. The remote effects of neonatal buspirone in these two mice strains presumably depend on genotype-related features of ontogeny of the 5-HT system.
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PMID:[Neonatal buspirone modulates the intermale aggression in adult mice]. 1702 93

The role of the monoamine neurotransmitter serotonin (5-HT) in the modulation of conspecific aggression in the fighting fish (Betta splendens) was investigated using pharmacological manipulations. We used a fish's response to its mirror image as our index of aggressive behavior. We also investigated the effects of some manipulations on monoamine levels in the B. splendens brain. Acute treatment with 5-HT and with the 5-HT1A receptor agonist 8-OH-DPAT both decreased aggressive behavior; however, treatment with the 5-HT1A receptor antagonist WAY-100635 did not increase aggression. Chronic treatment with the selective serotonin reuptake inhibitor fluoxetine caused no significant changes in aggressive behavior and a significant decline in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations. Treatment with the serotonin synthesis inhibitor p-chlorophenylalanine resulted in no change in aggression, yet serotonergic activity decreased significantly. Finally, a diet supplemented with L-tryptophan (Trp), the precursor to 5-HT, showed no consistent effects on aggressive behavior or brain monoamine concentrations. These results suggest a complex role for serotonin in the expression of aggression in teleost fishes, and that B. splendens may be a useful model organism in pharmacological and toxicological studies.
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PMID:Serotonin decreases aggression via 5-HT1A receptors in the fighting fish Betta splendens. 1755 55

Suicidal behavior is highly correlated with many emotional disturbances and some psychiatric disorders. The biogenic amine, serotonin, is one of the most important neurotransmitter in the central nervous system believed to play a huge role in pathogenesis of some kind of mental disorders. Drugs targeting serotonin receptors like serotonin reuptake inhibitors (SSRIs) are useful in the present therapy of anxiety and depression. Recent studies have reported that genetic factors are associated with development of some psychiatric disorders. Serotonin receptor single nucleotide polymorphism (SNP) has emerged as the subject of controversial result in correlation with suicide attempt. Further studies should be performed to confirm the influence of allelic variation of serotonin receptor on elevated risk of auto-aggression behavior. The aim of our study was to examine the frequency and genotype distribution of C(-1019)G polymorphism of regulatory region 5-HT1A receptor in the group of 65 suicide attempters and 63 persons in the control group. Using allele specific amplification PCR (ASA-PCR), we found that allele G was higher in suicidal attempters. The genotype frequency was significantly different between hospitalized patients and control subjects. The most common intoxication causes were antidepressants (56.9%), analgesics (18.5%) and cardiologic drugs (10.8%). Our data support hypothesis which indicate role of the 5-HT1A C(-1019)G SNP polymorphism in elevated risk of suicidal attempt.
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PMID:Association between 5-hydroxytryptamine 1A receptor gene polymorphism and suicidal behavior. 1772 68


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