Characterization of the discriminative stimulus properties induced by 5-HT1 and 5-HT2 agonists in rats.
The effect of different serotonin (5-HT) agonists and antagonists on the discriminative stimulus properties (cue) induced by 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT), 1-(m-trifluoromethylphenyl)piperazine (TFMPP) and d-LSD (d-lysergic acid diethylamide) has been investigated. The 8-OHDPAT cue was mimicked by the 5-HT1A agonists ipsapirone, buspirone, gepirone and partially by 5-methoxy-N,N-dimethyltryptamine and d-LSD. 5-HT1B (TFMPP and RU 24969) and 5-HT2 agonists (DOM, DOI and quipazine) were ineffective and induced disruption of responding. The 8-OHDPAT cue was antagonized by spiroxatrine and partially by (-)-alprenolol, whereas selective antagonists of 5-HT2 (ketanserin and ritanserin), 5-HT3 (ICS 205-930), alpha 1-adrenergic (prazosin) and beta-adrenergic receptors (ICI 118.551) were ineffective. The TFMPP cue was mimicked by RU 24969 and partially by quipazine. Other compounds were ineffective. Only (-)-alprenolol antagonized the effect of TFMPP. The d-LSD cue was mimicked by DOM, DOI, quipazine, 5-methoxy-N,N-dimethyltryptamine and partially by ipsapirone, TFMPP and RU 24969. The 3 latter compounds and 5-HT1A agonists induced disruption of responding. The d-LSD cue was antagonized by ketanserin and ritanserin, but not by the other antagonists mentioned above. The specific inhibitor of 5-HT uptake citalopram was not able to substitute for any of the 3 agonists. It is concluded that the drug discrimination technique can be used to identify selective agonists and antagonists of 5-HT receptor subtypes. Compounds with mixed effects on 5-HT receptor subtypes can also be identified. These show additional effects on reaction time and often disrupt responding at higher dosages.
Arnt
J
J
Department of Pharmacology, H. Lundbeck A/S, Valby, Denmark.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide