EFFECTS OF CHLORDIAZEPOXIDE, BUSPIRONE, AND SEROTONIN RECEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF SQUIRREL-MONKEYS MAINTAINED UNDER 2ND-ORDER SCHEDULES OF INTRAMUSCULAR COCAINE INJECTION OR FOOD PRESENTATION

被引:22
|
作者
NADER, MA [1 ]
BARRETT, JE [1 ]
机构
[1] UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BEHAV PHARMACOL LAB,BETHESDA,MD 20814
关键词
benzodiazepines; cocaine self‐administration; novel anxiolytics; schedule controlled behavior;
D O I
10.1002/ddr.430200103
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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‐HT1A) 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‐HT1b 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‐HT1 and 5‐HT2 receptors, produced large response rate increases in both groups of monkeys. Administration of the 5‐HT2 antagonist ketanserin (0.03‐3.0 mg/kg), the 5‐HT1A 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. Copyright © 1990 Wiley‐Liss, Inc.
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页码:5 / 17
页数:13
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