BEHAVIORAL EVIDENCE FOR A FUNCTIONAL INTERACTION BETWEEN CENTRAL 5-HT2-RECEPTOR AND 5-HT1A-RECEPTOR

The possibility of 5-HT2 receptor modulation of central 5-HT(1A) receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT(1A) receptor active drugs in rats. The 5-HT2/HT(IC) antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. Pretreatment with the 5-HT2/5-HT(1C) antagonist ICI 170,809 (0.25 - 5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. The 5-HT2/α1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of α1-adrenoceptors. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT(1A) agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT(1A) receptor-mediated function.