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Effects of chlordiazepoxide, buspirone, and serotonin receptor agonists and antagonists on responses of squirrel monkeys maintained under second‐order schedules of intramuscular cocaine injection or food presentation
Author(s) -
Nader Michael A.,
Barrett James E.
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430200103
Subject(s) - chlordiazepoxide , buspirone , ketanserin , agonist , pharmacology , chemistry , serotonin , 5 ht receptor , 5 ht1 receptor , inverse agonist , endocrinology , medicine , receptor , diazepam
Lever pressing of squirrel monkeys was maintained under second‐order schedules of either food presentation or cocaine injection. The first response after 3 min produced a 2 sec change in the color of a visual stimulus; the tenth stimulus presentation was followed by either an i.m. injection of cocaine (0.3, 1.0, or 2.0 mg/kg) or the delivery of food. The benzodiazepine chlordiazepoxide (0.3‐5.6 mg/kg) increased responding maintained by food at doses that decreased cocaine‐maintained responding. In contrast, buspirone, a novel nonbenzodiazepine anxiolytic (0.001‐0.03 mg/kg), its analog gepirone (0.003‐0.03 mg/kg), and the N serotonin 1A (5‐HT 1A ) agonist 8‐hydroxy‐2(di‐ n ‐propylamino)tetralin (8‐OH‐DPAT; 0.0003‐0.001 mg/kg) increased cocaine‐maintained responding at doses that decreased responding maintained by food. The inverse agonist at benzodiazepine receptors β‐carboline‐3‐carboxylic acid ethyl ester (βCCE) only decreased response rates irrespective of the maintaining event. m‐Chlorophenylpiperazine (mCPP), an agonist at 5‐HT 1b receptors, increased responding maintained by food while only decreasing cocaine maitained responding (0.001‐0.03 mg/kg), whereas metergoline (0.1‐0.3 mg/kg), a serotonin antagonist with affinity for both 5‐HT 1 and 5‐HT 2 receptors, produced large response rate increases in both groups of monkeys. Administration of the 5‐HT 2 antagonist ketanserin (0.03‐3.0 mg/kg), the 5‐HT 1A compound spiroxatrine (0.0003‐0.03 mg/kg), or the nonselective 5‐HT agonist quipazine (0.003‐1.0 mg/kg) resulted in dose‐dependent response rate decreases in both groups. These results further differentiate buspirone and related compounds from typical anxiolytics and suggest a differential involvement of 5‐HTIA receptors in behaviors maintained by cocaine or food presentation.