Behavioural evidence for a functional interaction between central 5‐HT2 and 5‐HT1A receptors

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Abstract
1 The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2 The 5-HT2/5-HT1C 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. 3 Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25–5 mg kg−1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4 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. 5 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. 6 Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7 We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function.