On the Functional Cross-Talk between Brain 5-HT1A and 5-HT2A Receptors.
We have found that activation of 5-HT1A receptor with 8-OH-DPAT (0.1, 0.5 and 1.0 mgkg, i. p.) considerably and dose-dependently reduced the number of 5-HT2A receptor-mediated head-twitches, whereas 5-HT1A receptor blockade with WAY-100635 (0.5 and 1.0 mgkg, i. p.), on the contrary, pro- duced significant enhancement of this 5-HT2A receptor functional response. At the same time 5-HTA receptor activation with DOI (0.5 and 1.0 mgkg, i. p.) abolished the 5-HT1A receptor-mediated hypothermic reaction, whereas 5-HT2A receptor blockade with ketanserin (1.0 and 2.0 mgkg, i. p.) increased this 5-HT1A receptor functional response. Moreover, we revealed that 5-HT2A receptor antagonist ketanserin (1.0 and 2.0 mgkg, i. p. or 20 and 40 nmol, i. c. v.) produced the considerable dose-dependent hypothermia. This ketanserin-induced (40 nmol, i. c. v.) hypothermic reaction was significantly attenuated by pretreatment with 5-HT1A receptor antagonist WAY-100635 (1.0 mgkg, i. p.), indicating that 5-HT2A receptor-related hypothermic response is mediated, at least partially, via activation of 5-HT1A receptors. The obtained data indicate that 5-HTA and 5-HT2A receptors are able to modulate each other functional activity by means of bilateral functional cross-talk.