Comparison of effects of buspirone and gepirone with benzodiazepines and antagonists of dopamine and serotonin receptors on punished behavior of rats.
Lever-press responding of male Sprague-Dawley rats was maintained under a conflict procedure in which every tenth response produced both food and electric shock (punished responding); every thirtieth response produced only food in the presence of a separate stimulus. The benzodiazepines, diazepam and chlordiazepoxide, increased responding 4- to 6-fold. Buspirone and its structural analog, gepirone, only moderately and inconsistently increased responding (1.5- and 2-fold, respectively). The dopamine-2 (D-2) receptor antagonist, sulpiride, but not haloperidol had effects similar to buspirone. The D-1 antagonist SCH 23390 was not active. The non-selective serotonin (5HT) antagonists, cyproheptadine and methysergide, consistently increased responding 2-fold, but the 5HT-2 antagonists, ketanserin, pirenperone, ritanserin, R-56 413, and LY 53857 and the 5HT-1A agonist, 8-OH-DPAT, were inactive. In pigeons, serotonergic compounds have been shown to increase punished responding. The present results suggest that exploitation of this species difference may be helpful in evaluating new chemicals for novel anxiolytic activity and for investigation of their mechanisms of action.
Psychobiology Laboratory, NIDA Addiction Research Center, Baltimore, MD 21224, USA.
J.M.
JM
Witkin
L.A.
LA
Perez