Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats
Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats
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DOI：
10.1007/s002130000676
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发表时间：
2001-04-01
影响因子：
3.4
通讯作者：
Neisewander, JL
中科院分区：
文献类型：
--
作者：
Baker, DA;Tran-Nguyen, LTL;Neisewander, JL
理由：临床研究检验选择性血清素再摄取抑制剂氟西汀的功效。减少对可卡因的渴望和使用的效果不一致。目的：更好地了解氟西汀治疗对可卡因激励动机的影响。本研究评估了慢性氟西汀治疗对暴露于可卡因自我给药环境或可卡因预注射后的大鼠寻求可卡因行为的影响。方法：训练大鼠按下可卡因强化剂的杠杆（每 0.1 毫升 0.5 毫克/千克，静脉注射）或接受盐水的结合给药。然后，他们退出该治疗方案，并每天注射 20 次盐水或氟西汀（3.0 mg/kg，IP）。最后一次注射后 24 小时，将大鼠置于自我给药环境中，测量可卡因寻求行为（即非强化杠杆按压）90 分钟。然后在注射盐水后 60 分钟和在注射可卡因启动注射（15 毫克/千克，IP）后 90 分钟测量已熄灭的可卡因寻求行为的恢复情况。结果：长期氟西汀治疗减弱了大多数大鼠（n = 16）暴露于自我给药环境后的可卡因寻求行为，但增强了两只大鼠的可卡因寻求行为。此外。该治疗未能改变可卡因启动注射后的可卡因寻求行为。有趣的是，自我给药训练期间可卡因的摄入量与可卡因启动注射后的可卡因寻求行为相关。事实上，启动注射仅在可卡因摄入量高（而不是低）的大鼠中恢复了可卡因寻求行为（基于中位数分裂）。结论：这些结果表明，当动物处于无可卡因状态时，长期氟西汀治疗会降低可卡因的动机。此外，可卡因使用的个体差异与对可卡因启动的激励作用的敏感性的个体差异有关。
Rationale: Clinical studies examining the efficacy of the selective serotonin reuptake inhibitor, fluoxetine. in decreasing craving and cocaine use have been inconsistent. Objective: To understand better the effects of fluoxetine treatment on incentive motivation for cocaine. the present study assessed the effects of chronic fluoxetine treatment on cocaine-seeking behavior in rats following exposure to a cocaine self-administration environment or a cocaine priming injection, Methods: Rats were trained to press a lever for a cocaine reinforcer (0.5 mg/kg per 0.1 ml, IV) or received yoked administration of saline. They were then withdrawn from this regimen and given 20 daily injections of saline or fluoxetine (3.0 mg/kg, IP). Twenty-four hours after the last injection, the rats were placed in the self-administration environment and cocaine-seeking behavior (i.e., non-reinforced lever pressing) was measured for 90 min. Reinstatement of extinguished cocaine-seeking behavior was then measured for 60 min following a saline injection and for 90 min following a cocaine priming injection (15 mg/kg, IP). Results: Chronic fluoxetine treatment attenuated cocaine-seeking behavior following exposure to the self-administration environment in most rats (n=16), but enhanced cocaine-seeking behavior in two rats. Furthermore. the treatment failed to alter cocaine-seeking behavior following a cocaine priming injection. Interestingly, the amount of cocaine intake during self-administration training correlated with cocaine-seeking behavior following the cocaine priming injection. In fact, the priming injection reinstated cocaine-seeking behavior only in rats with high, but not low, cocaine intake based on a median split. Conclusions: These results suggest that chronic fluoxetine treatment decreases motivation for cocaine when animals are in a cocaine-free state. Furthermore, individual differences in cocaine use are related to individual differences in sensitivity to incentive motivational effects of cocaine priming.