Characterization of the Discriminative Stimulus Properties Induced by 5‐HT1and 5‐HT2Agonists in Rats

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Abstract
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‐HT1Aagonists ipsapirone, buspirone, gepirone and partially by 5‐methoxy‐N,N‐dimethyltryptamine and d‐LSD. 5‐HT1B(TFMPP and RU 24969) and 5‐HT2agonists (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), α1‐adrenergic (prazosin) and β‐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‐HT1Aagonists 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.