CHARACTERIZATION OF 5-HT(6) RECEPTOR AND EXPRESSION OF 5-HT(6) MESSENGER-RNA IN THE RAT-BRAIN DURING ONTOGENIC DEVELOPMENT

We have determined the pharmacological characteristics of the rat 5-ht (6) receptor stably expressed in CHO cells. Moreover, using RT-PCR exp eriments the in vivo expression of the gene encoding this receptor was studied in rat at Various embryonic days (ED) starting from ED10 to b irth (PN0) and at post-natal days (PN) up to PN36 The pharmacological analysis of the [H-3]5-HT binding in stably transfected CHO cells expr essing rat 5-ht(6) receptors revealed the presence of a single class o f high affinity saturable binding sites for 5-HT corresponding to an a ffinity constant: Kd = 27.2+/-3.4 nM. This receptor also exhibited a h igh affinity for a number of typical and atypical antipsychotics, tric yclic antidepressant drugs and ergot alkaloids. In stably transfected CHO cells, serotonin elicited a potent stimulation of adenylyl cyclase activity which was blocked by antipsychotic and antidepressant drugs. These results confirm the hypothesis that 5-ht(6) receptors may corre spond to an important target for atypical antipsychotics and reveal an original pharmacological profile for this receptor. The study of the ontogeny of the 5-ht(6) mRNA in rat developing brain showed that 5-ht( 6) mRNA were first detectable with a high level on ED12, slightly decr eased up to ED17 and then remained stable at high level until the adul t age. The ontogenetic pattern of 5-ht(6) mRNA expression appeared to correlate with the occurence of the first cell bodies of serotonergic neurons; the early expression of 5-ht(6) mRNA and the fact that this r eceptor is positively coupled to the production of cAMP may suggest a role for 5-ht(6) receptor in the early growth process involving the se rotonergic system.