Mcgeehan Andrew J, Olive Michael Foster
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, California, USA.
Behav Pharmacol. 2006 Jun;17(4):363-7. doi: 10.1097/01.fbp.0000224384.01863.5f.
Acamprosate (calcium acetylhomotaurinate) is a glutamatergic neuromodulator efficacious at reducing relapse in alcoholic patients. The effect of acamprosate on relapse to other drugs of abuse has received little attention, however, and given increasing evidence that glutamatergic transmission mediates relapse to cocaine-seeking behavior, the purpose of this study was to assess the effects of acamprosate on the reinstatement of a conditioned place preference for cocaine. Mice were conditioned daily with cocaine (15 mg/kg), tested for the establishment of cocaine conditioned place preference, and then retested once weekly to monitor the extinction of the place preference. Following extinction of cocaine conditioned place preference, animals were treated daily with saline or acamprosate (30 or 100 mg/kg) for 3 days, followed by a single injection of cocaine (15 mg/kg) to reinstate conditioned place preference. In mice treated with saline or the low (30 mg/kg) dose of acamprosate, cocaine induced a significant reinstatement of the previously extinguished conditioned place preference; however, this reinstatement was not observed in mice treated with the high (100 mg/kg) dose of acamprosate. These results indicate that acamprosate can attenuate relapse-like behavior in mice and suggest that this compound may be potentially useful in the treatment for cocaine addiction.
阿坎酸（钙乙酰高牛磺酸）是一种谷氨酸能神经调节剂，对减少酒精依赖患者的复发有效。然而，阿坎酸对其他滥用药物复发的影响鲜受关注，而且鉴于越来越多的证据表明谷氨酸能传递介导了对可卡因觅药行为的复发，本研究的目的是评估阿坎酸对可卡因条件性位置偏爱恢复的影响。小鼠每天用可卡因（15毫克/千克）进行条件化训练，测试可卡因条件性位置偏爱的建立，然后每周重新测试一次以监测位置偏爱的消退。在可卡因条件性位置偏爱消退后，动物每天用生理盐水或阿坎酸（30或100毫克/千克）处理3天，随后单次注射可卡因（15毫克/千克）以恢复条件性位置偏爱。在用生理盐水或低剂量（30毫克/千克）阿坎酸处理的小鼠中，可卡因显著恢复了先前消退的条件性位置偏爱；然而，在用高剂量（100毫克/千克）阿坎酸处理的小鼠中未观察到这种恢复。这些结果表明阿坎酸可以减轻小鼠的复发样行为，并表明该化合物可能对可卡因成瘾的治疗有潜在用途。
