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)

Hypo- and hyperthermic responses resulting from the activation of putative 5-HT1A and 5-HT2 receptors, respectively, were examined after the chronic treatment of rats with monoamine oxidase inhibitors. The treatment of rats for 4 or 7 days with nialamide (40 mg/kg, twice daily) resulted in a suppression of the hypothermic effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05-0.25 mg/kg, SC). The decrease in body temperature elicited by a low dose of 5-methoxy-N, N-dimethyltryptamine (5MeODMT, 1 mg/kg) also was diminished in rats treated chronically with nialamide. The administration of a high dose of 5MeODMT (5 mg/kg) resulted in a hyperthermic response, which was also attenuated after the repeated administration of nialamide. The repeated administration of clorgyline (a selective inhibitor of type A MAO) or deprenyl (a selective inhibitor of type B MAO) failed to alter the hypothermic effect of 8-OH-DPAT. However, in animals treated chronically with both clorgyline and deprenyl, a suppressed response to 8-OH-DPAT was observed. In view of the concept that the hypo- and hyperthermic responses to 5-HT agonists are mediated by 5-HT1A and 5-HT2 receptor subtypes, respectively, it is concluded that the responsiveness of these 5-HT receptor subtypes involved in thermoregulatory responses is decreased following chronic treatment of rats with monoamine oxidase inhibitors. It appears that inhibition of both type A and B MAO is necessary for this desensitization process.
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PMID:Suppression of the hypo- and hyperthermic responses to 5-HT agonists following the repeated administration of monoamine oxidase inhibitors. 294 56

An involvement of serotonin (5-HT) 1A receptors in the etiology of psychiatric disorders has been suggested. Hypo-responsiveness of the 5-HT1A receptor is linked to anxiety and constitutive deletion of the 5-HT1A receptor produces anxiety-like behaviors in the mouse. Evidence that 5-HT1A receptor inactivation increases the therapeutic effects of antidepressants has also been presented. The present studies used in vivo microdialysis and homologous recombination techniques to examine the contribution of 5-HT1A autoreceptors to these effects. Basal and fluoxetine-evoked extracellular concentrations of 5-HT were quantified in the striatum, a projection area of dorsal raphe neurons (DRN), of wild-type (WT) and 5-HT1A receptor knock out (KO) mice. The density of 5-HT transporters was also determined. Basal 5-HT concentrations did not differ in WT and KO mice. Fluoxetine (10 mg/kg) increased 5-HT concentrations in both genotypes. This increase was, however, 2-fold greater in KO mice. In contrast, no differences in K(+)-evoked 5-HT concentrations were seen. Similarly, neither basal nor stimulation-evoked DA differed across genotype. Autoradiography revealed no differences between genotype in the density of 5-HT transporters or post-synaptic 5-HT2A receptors, an index of 5-HT neuronal activity. These experiments demonstrate that, under basal and KCl stimulated conditions, adaptive mechanisms in the 5-HT system compensate for the lack of 5-HT1A autoreceptor regulation of DRN. Furthermore, they suggest that the absence of release-regulating 5-HT1A autoreceptors in the DRN can not account for the anxiety phenotype of KO mice. The enhanced response to fluoxetine in KO mice is consistent with pharmacological studies and suggests that adaptive mechanisms that occur in response to 5-HT1A receptor deletion are insufficient to oppose increases in 5-HT concentrations produced by acute inhibition of the 5-HT transporter.
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PMID:Differential effects of 5-HT1A receptor deletion upon basal and fluoxetine-evoked 5-HT concentrations as revealed by in vivo microdialysis. 1137 90