Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT1A and 5-HT2A receptors functional activity and expression of key genes of the brain serotonin system |
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Authors: | Elena M Kondaurova Vladimir S NaumenkoNina K Popova |
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Institution: | Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia |
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Abstract: | Among serotonin (5-HT) receptors, the 5-HT3 receptor is the only ligand-gated ion-channel. Little is known about the interaction between the 5-HT3 receptor and other 5-HT receptors and influence of 5-HT3 chronic activation on other 5-HT receptors and the expression of key genes of 5-HT system. Chronic activation of 5-HT3 receptor with intracerebroventricularly administrated selective agonist 1-(3-chlorophenyl)biguanide hydrochloride (m-CPBG) (14 days, 40 nmol, i.c.v.) produced significant desensitization of 5-HT3 and 5-HT1A receptors. The hypothermic responses produced by acute administration of selective agonist of 5-HT3 receptor (m-CPBG, 40 nmol, i.c.v.) or selective agonist of 5-HT1A receptor (8-hydroxy-2-(di-n-propylamino)tetralin) (8-OH-DPAT, 1 mg/kg, i.p.) was significantly lower in m-CPBG treated mice compared with the mice of control groups. Chronic m-CPBG administration failed to induce any significant change in the 5-HT2A receptor functional activity and in the expression of the gene encoding 5-HT2A receptor. Chronic activation of 5-HT3 receptor produced no considerable effect on the expression on 5-HT3, 5-HT1A, and 5-HT transporter (5-HTT) and tryptophan hydroxylase-2 (TPH-2) genes – the key genes of brain 5-HT system, in the midbrain, frontal cortex and hippocampus. In conclusion, chronic activation of ionotropic 5-HT3 receptor produced significant desensitization of 5-HT3 and postsynaptic 5-HT1A receptors but caused no considerable changes in the expression of key genes of the brain 5-HT system. |
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Keywords: | Brain 5-HT3 5-HT1A 5HT2A serotonin receptors Receptors functional activity Expression of the 5-HT3 5-HT1A 5HT2A 5-HTT TPH-2 genes |
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