Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors.
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-HTIC 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/alpha 1-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 alpha 1-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.
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MRC Unit, Radcliffe Infirmary, Oxford.
Sharp
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Grahame-Smith
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin; D012701:Serotonin / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D010880:Piperidines; D011743:Pyrimidines; D011804:Quinolines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C060632:ICI 170809; D007650:Ketanserin; D006220:Haloperidol; C039979:gepirone; D001058:Apomorphine; D011224:Prazosin