Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT(1A) and 5-HT(2A) receptors functional activity and expression of key genes of the brain serotonin system.
Among serotonin (5-HT) receptors, the 5-HT(3) receptor is the only ligand-gated ion-channel. Little is known about the interaction between the 5-HT(3) receptor and other 5-HT receptors and influence of 5-HT(3) chronic activation on other 5-HT receptors and the expression of key genes of 5-HT system. Chronic activation of 5-HT(3) 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-HT(3) and 5-HT(1A) receptors. The hypothermic responses produced by acute administration of selective agonist of 5-HT(3) receptor (m-CPBG, 40 nmol, i.c.v.) or selective agonist of 5-HT(1A) receptor (8-hydroxy-2-(di-n-propylamino)tetralin) (8-OH-DPAT, 1mg/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-HT(2A) receptor functional activity and in the expression of the gene encoding 5-HT(2A) receptor. Chronic activation of 5-HT(3) receptor produced no considerable effect on the expression on 5-HT(3), 5-HT(1A), 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-HT(3) receptor produced significant desensitization of 5-HT(3) and postsynaptic 5-HT(1A) receptors but caused no considerable changes in the expression of key genes of the brain 5-HT system.
Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Science, Novosibirsk, Russia. kond_em@bionet.nsc.ru
Elena M
EM
Kondaurova
Vladimir S
VS
Naumenko
Nina K
NK
Popova
D000818:Animals; D001645:Biguanides / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics / Q000502:physiology*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology*
D001645:Biguanides; D044402:Receptor, Serotonin, 5-HT2A; D044406:Receptors, Serotonin, 5-HT3; D058827:Serotonin 5-HT3 Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C065734:1-(3-chlorophenyl)biguanide