Clark A, Lindgren S, Brooks S P, Watson W P, Little H J
Drug Dependence Unit, Psychology Department, Durham University, South Road, Durham DH1 3LE, UK.
Neuropharmacology. 2001 Jul;41(1):108-17. doi: 10.1016/s0028-3908(01)00037-5.
Effects of nicotine, administered by continuous infusion via osmotic minipumps, were studied on the operant self-administration of alcohol by rats, using a variable interval (15 s) schedule, and measuring the acquisition, maintenance, extinction and reinstatement of responding for alcohol. Doses of nicotine of 0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant increase in responding on the lever delivering the reward when water was substituted for the alcohol, indicating delayed extinction of responding. During infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over the "sucrose-fading" training sessions, during acquisition of responding, when mixtures of alcohol and sucrose were provided as reward. When minipumps infusing 2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been acquired, the responding for alcohol increase during the first week of nicotine infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no significant effects. The results indicate that nicotine can increase operant responding for alcohol and this is crucially dependent on the dose of nicotine and the time of testing. The results have implications for the frequently encountered dependence on the combination of alcohol and nicotine.
通过渗透微型泵持续输注尼古丁，研究其对大鼠酒精操作性自我给药的影响，采用可变间隔（15秒）时间表，并测量对酒精反应的习得、维持、消退和恢复情况。剂量为0.25、1.25和7.5毫克/千克/24小时的尼古丁对酒精反应的维持没有显著影响，但5毫克/千克/24小时的尼古丁在用水替代酒精时，导致在提供奖励的杠杆上的反应显著增加，表明反应的消退延迟。在输注2.5毫克/千克/24小时尼古丁期间，在“蔗糖递减”训练阶段，即当提供酒精和蔗糖混合物作为奖励来习得反应时，反应显著增强。当在获得酒精反应后植入输注2.5毫克/千克/24小时尼古丁的微型泵时，在尼古丁输注的第一周对酒精的反应增加，但相应剂量为0.25、1.25和7.5的尼古丁输注没有显著影响。结果表明，尼古丁可增加对酒精的操作性反应，这关键取决于尼古丁的剂量和测试时间。这些结果对于经常遇到的酒精和尼古丁联合依赖情况具有启示意义。
