Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat.
The 5-HT receptor subtypes involved in the mediation of reciprocal forepaw treading and the flat body posture induced by the central 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), were examined in intact rats and in rats depleted of monoamines with reserpine. Forepaw treading in non-reserpinised rats was antagonised by the 5-HT2 receptor antagonist, ketanserin, only at doses in excess of those required for occupation of a large proportion of 5-HT2 receptors in brain, and at which there was significant inhibition of stereotyped sniffing induced by the dopamine receptor agonist, apomorphine. Since forepaw treading induced by 5-MeODMT was also blocked in intact rats by haloperidol, blockade of the behaviour by ketanserin may more accurately reflect antagonism at dopamine receptors than at 5-HT2 receptors. In reserpinised rats, i.e. with minimised contributions from other monoamine systems, neither forepaw treading nor the flat body posture were significantly altered by ketanserin, haloperidol or the beta 1- and beta 2-selective adrenoceptor antagonists, betaxolol and ICI 118.551, making a key role for 5-HT2 receptors, dopamine receptors and beta-adrenoceptors unlikely. In contrast, forepaw treading in both reserpinised and non-reserpinised rats was antagonised stereoselectively by pindolol and by spiperone, which interact with 5-HT1 and 5-HT1A recognition sites. The results are consistent with the hypothesis that forepaw treading induced by 5-MeODMT arises by activation of the putative 5-HT1A receptor. Antagonism of the flat body posture by pindolol could be demonstrated only in non-reserpinised rats and the mechanism of induction of this behaviour remains to be established.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015784:Betaxolol; D006220:Haloperidol / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D010880:Piperidines; D011412:Propanolamines; D011985:Receptors, Serotonin; C026777:ICI 118551; D013134:Spiperone; D012110:Reserpine; D007650:Ketanserin; D010869:Pindolol; D006220:Haloperidol; D001058:Apomorphine; D015784:Betaxolol; D011224:Prazosin