In this study we examined the effects of 5-HT(1A) ligands in rats trained to discriminate 0.18 mg/kg i.p. 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT) from saline in a two-lever, fixed ratio (FR)10 schedule of food reinforcement, and in pigeons trained to discriminate 0.31 mg/kg i.m. 8-OH-DPAT from saline in a two-key, FR30 schedule of food reinforcement. In both species, 8-OH-DPAT and a variety of structurally unrelated 5-HT(1A) ligands occasioned dose-related, relatively high levels of drug-appropriate selection (i.e. ≤67%). A significant positive correlation was found between estimated ED50 values in both species (r = 0.84, P < .001). Further, 5-HT(1A) antagonists, NAN-190, penbutolol, (-)-pindolol, tertatolol and WAY-100635, produced dose-related decreases in 8-OH-DPAT- appropriate selection, and their potencies for antagonism in rats and pigeons were highly correlated (r = 0.96, P < .01). The potency of WAY 100635 in rats and pigeons was quantified by Schild analysis (apparent in vivo pA2 values: 7.8 vs. 8.3, rat vs. pigeon, respectively). Although most 5-HT(1A) agonists produced similar 8-OH-DPAT-like discriminative stimulus effects in bow species, two compounds, lisuride and eltoprazine, occasioned high levels of drug-appropriate selection in pigeons, but not in rats. In contrast, idazoxan, yohimbine, LEK 8804 and BMY 7378 produced greater effects in rats. Among this latter group of compounds, only BMY 7378 blocked the discriminative stimulus effects of 8-OH-DPAT in pigeons, which suggested that intermediate levels of drug-appropriate selection observed with the remaining compounds are not necessarily the result of low intrinsic activity. Overall, these results demonstrate similarities in the discriminative stimulus effects of 8-OH-DPAT in rats and pigeons despite different training conditions (e.g., training dose and route of administration). Even so, the finding that some 5- HT(1A) ligands did not produce similar effects in rats and pigeons illustrates the need to examine possible 8-OH-DPAT-like discriminative stimulus effects of compounds in both species.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1998|
ASJC Scopus subject areas
- Molecular Medicine