Receptor-genes cross-talk: effect of chronic 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin treatment on the expression of key genes in brain serotonin system and on behavior

• Published in: Neuroscience Vol. 169; no. 1; pp. 229 - 235
• Main Authors: Popova, N.K, Naumenko, V.S, Cybko, A.S, Bazovkina, D.V
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 11.08.2010
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin; Neurology; 5-HT transporter; chronic 8-OH-DPAT treatment; 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane; tryptophan hydroxylase-2; DNA-dependent RNA-polymarese II; 8-OH-DPAT; 8-hydroxy-2-(di-n-propylamino)tetralin; 5-HTT; 5-HT 2A receptors; rPol II; TPH-2; tryptophan hydroxylase-2 genes expression; behavior; 5-HT 1A; DOI
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.04.044

Abstract Dysfunction in brain serotonin (5-HT) system has been implicated in the psychopathology of anxiety, depression, drug addiction, and schizophrenia. The 5-HT1A receptors play a central role in the control of 5-HTergic neurotransmission. There are some scarce data showing cross-regulation between 5-HT receptors. Here, we investigated whether interaction exists between 5-HT1A receptor and genes encoding key members in brain 5-HT system. Chronic treatment with selective agonist of 5-HT1A receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) produced considerable decrease in hypothermic response to acute administration of 8-OH-DPAT in CBA/Lac mice indicating desensitization of 5-HT1A receptors. The decrease in 5-HT1A gene expression as well as decrease in the expression of gene encoding key enzyme in 5-HT synthesis, tryptophan hydroxylase-2 (TPH-2) in the midbrain, and the expression of the gene encoding 5-HT2A receptor in the frontal cortex was shown. There were no significant changes in 5-HT transporter mRNA level in the midbrain. Despite considerable decrease in the expression of the genes encoding tryptophan hydroxylase-2, 5-HT1A and 5-HT2A receptors, chronic 8-OH-DPAT treatment failed to produce significant changes in 5-HT1A -linked behavior (intermale aggression, open-field behavior, light-dark box, and pinch-induced catalepsy), suggesting compensatory and adaptive effect of genes suppression. The obtained data on the effect of 8-OH-DPAT-induced desensitization of 5-HT1A receptors on 5-HT1A , 5-HT2A and TPH-2 gene expression demonstrated the role of 5-HT1A receptor as indirect regulator of gene expression. The results provide the first evidence of receptor-key genes interaction in brain 5-HT system and may have profound implications in understanding the functioning of the brain neurotransmitter systems.