MONOAMINE REUPTAKE INHIBITORS ENHANCE THE DISCRIMINATIVE STATE INDUCED BY COCAINE IN THE RAT
MONOAMINE REUPTAKE INHIBITORS ENHANCE THE DISCRIMINATIVE STATE INDUCED BY COCAINE IN THE RAT
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DOI：
10.1007/bf02244175
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发表时间：
1991-01-01
影响因子：
3.4
通讯作者：
CALLAHAN, PM
中科院分区：
文献类型：
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作者：
CUNNINGHAM, KA;CALLAHAN, PM
可卡因抑制多巴胺(DA)、去甲肾上腺素(NE)和5-羟色胺(5-HT)的再摄取。为了研究这种再摄取过程在可卡因的辨别刺激特性中的相对作用，对雄性大鼠(N=16)进行了两级水强化药物辨别任务中对可卡因(10 mg/kg)和生理盐水的辨别训练，并在替代或组合测试中给予神经活性化合物。DA再摄取抑制剂GBR 12909(2-16 mg/kg)完全模拟可卡因。去甲肾上腺素(地塞帕明，2-8 mg/kg)和5-羟色胺(氟西汀，0.625-5 mg/kg)的再摄取抑制剂不能替代训练药物。小剂量地塞帕明(3 mg/kg)、氟西汀(1.2 5 mg/kg)或GBR 12909(2 mg/kg)与小剂量可卡因(0.625-2.5 mg/kg)合用可增强这种精神刺激剂的辨别刺激特性。在地塞帕明(0.38 mg/kg)、氟西汀(0.79 mg/kg)或GBR 12909(0.84 mg/kg)的存在下，预测引起50%药物水平反应的剂量(ED50)比在没有任何再摄取抑制剂的情况下可卡因的ED50(1.57 mg/kg)减少。GBR 12909模拟可卡因线索的发现证实了可卡因的刺激特性主要由DA系统介导的假说。单胺再摄取抑制剂在大鼠体内增强了可卡因的刺激作用，这表明这些药物也可以放大可卡因对人类的主观影响，考虑到目前抗抑郁药在治疗可卡因滥用者中的使用情况，应该考虑这种可能性。
Cocaine inhibits the reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). To investigate the relative role of such reuptake processes in the discriminative stimulus properties of cocaine, male rats (N = 16) were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced drug discrimination task and were administered neuroactive compounds during substitution or combination tests. The DA reuptake inhibitor GBR 12909 (2-16 mg/kg) completely mimicked cocaine. The reuptake inhibitors for NE (desipramine; 2-8 mg/kg) and 5-HT (fluoxetine; 0.625-5 mg/kg) did not substitute for the training drug. A low dose of either desipramine (3 mg/kg), fluoxetine (1.25 mg/kg), or GBR 12909 (2 mg/kg) coadministered with low doses of cocaine (0.625-2.5 mg/kg) enhanced the discriminative stimulus properties of this psychostimulant. The dose predicted to elicit 50% drug-lever responding is reduced (ED50) in the presence of desipramine (0.38 mg/kg), fluoxetine (0.79 mg/kg) or GBR 12909 (0.84 mg/kg) compared to the ED50 for cocaine (1.57 mg/kg) in the absence of any reuptake inhibitor. The finding that GBR 12909 mimics the cocaine cue corroborates the hypothesis that the stimulus properties of cocaine are mediated predominantly by DA systems. The potentiation of the stimulus effects of cocaine by monoamine reuptake inhibitors in rats suggests that these drugs could also amplify the subjective effects of cocaine in humans, a possibility that should be considered given the current use of antidepressants in the treatment of cocaine abusers.