The serotonin (5-HT) receptor-related compounds metergoline, pirenperone, ketanserin, cyproheptadine, pizotyline, methysergide, lysergic acid diethylamide, mianserin and cinanserin were studied in pigeons trained to discriminate I-5-hydroxytryptophan (I-5-HTP) (18.0 mg/kg) from saline and in pigeons trained to discriminate quipazine (1.0 mg/kg) from saline. Metergoline did not generalize to either quipazine or I-5-HTP but did antagonize drug-appropriate responding in both groups. Ketanserin potently blocked the quipazine discriminative stimulus and neither generalized to nor attenuated the I-5-HTP discriminative stimulus. Pirenperone, cinanserin, cyproheptadine, methysergide, pizotyline and mianserin attenuated the quipazine discriminative stimulus at low doses and, at higher doses, generalized to the I-5-HTP discriminative stimulus. No antagonism of the I-5-HTP-discriminative stimulus or generalization to the quipazine-discriminative stimulus were observed with these compounds. A correlation coefficient of 0.93 was calculated between the potencies of 5-HT compounds to generalize to the I-5-HTP stimulus and the binding affinities of these compounds for a 5-HT1 receptor in rat brain. In addition, a correlation coefficient of 0.78 was calculated between the potencies of 5-HT compounds to attenuate the quipazine stimulus and the binding affinities of these compounds for the 5-HT2 receptor in rat brain. These observations suggest cyproheptadine, pizotyline, methysergide, lysergic acid diethylamide, mianserin and cinanserin are agonists at the 5-HT1 receptor in the I-5-HTP discrimination and antagonists at a 5-HT2 receptor in the quipazine discrimination in pigeons.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1991|
ASJC Scopus subject areas
- Molecular Medicine