期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 80, 期 2, 页码 297-307出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2004.12.001
关键词
5-HT1B receptor; RU24969; GR127935; reinstatement; incentive motivation; relapse
资金
- NIDA NIH HHS [DA11064] Funding Source: Medline
Serotonin systems have been implicated in incentive motivation for cocaine, yet little is known about the role of 5-HT1B/1A receptors in these processes. We used the extinction/reinstatement model to examine the effects of the 5-HT1B/1A receptor agonist, RU24969, on reinstatement of extinguished cocaine-seeking behavior. Rats trained to self-administer cocaine subsequently underwent extinction. They were then tested twice for cue and cocaine-primed reinstatement of extinguished cocaine-seeking behavior, receiving saline pretreatment I day and their assigned dose of RU24969 (0.3, 1.0, 3.0 mg/kg) the other day. Rats were later trained on a schedule of sucrose reinforcement in novel chambers and then tested for effects of RU24969 on cue reinstatement of sucrose-seeking behavior and locomotion. RU24969 decreased cue and cocaine reinstatement of cocaine-seeking behavior and cue reinstatement of sucrose-seeking behavior. Locomotion was increased only at the highest RU24969 dose (3 mg/kg). A subsequent experiment demonstrated that the effects of RU24969 (1 mg/kg) on extinguished cocaine-seeking behavior were reversed by the 5-HT1B antagonist GR127935 (3 mg/kg). These findings suggest that the effects of RU24969 on cue and cocaine reinstatement of cocaine-seeking behavior are 5-HT1B receptor-mediated. Overall, the results suggest that stimulation of 5-HT1B receptors may produce a general decrease in motivation. (C) 2004 Elsevier Inc. All rights reserved.
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