Winger Gail, Galuska Chad M, Hursh Steven R
Department of Pharmacology, University of Michigan, 1301 MSRB III, Ann Arbor, MI 48109-0632, USA.
Psychopharmacology (Berl). 2007 Sep;193(4):587-98. doi: 10.1007/s00213-007-0809-9. Epub 2007 May 18.
Although ethanol is frequently used in combination with other psychoactive drugs, the behavioral and pharmacological reasons for this form of polydrug abuse have not been well described.
Rhesus monkeys with indwelling intravenous catheters produced intravenous injections of ethanol (50, 100, or 200 mg/kg/inj), flunitrazepam (0.001-0.03 mg/kg/inj), cocaine (0.01 or 0.03 mg/kg/inj), or combinations of ethanol and these drugs or gammahydroxybutyrate (GHB) (1.0 or 3.2 mg/kg/inj) by lever pressing according to a fixed-ratio schedule. The response requirement for each drug or drug combination was increased across sessions (10, 32, 100, 320, or 1,000). The dependent variables were rates of responding maintained by the drug or drug combination and the elasticity of drug demand when consumption was expressed as a function of price.
Elasticity (P (max)) values for each drug varied among the monkeys but retained the same rank order for the monkeys, suggesting a fundamental difference in the animals' apparent sensitivities to the reinforcing effects of the drugs. Combining ethanol with the other drugs did not increase their reinforcing effectiveness. GHB (ineffective in previous studies) did not modify ethanol's reinforcing effects; demand functions for the combination of ethanol and flunitrazepam were slightly less elastic than for ethanol alone, but no different from that for flunitrazepam alone; adding ethanol to cocaine detracted from the reinforcing effectiveness of cocaine.
The hypothesis that use of ethanol in combination with sedative and stimulant drugs is due to an ability of ethanol to enhance the reinforcing effects of these drugs is not supported.
尽管乙醇经常与其他精神活性药物联合使用,但这种多药滥用形式的行为和药理学原因尚未得到充分描述。
通过留置静脉导管的恒河猴根据固定比率程序按压杠杆进行静脉注射乙醇(50、100或200毫克/千克/注射)、氟硝西泮(0.001 - 0.03毫克/千克/注射)、可卡因(0.01或0.03毫克/千克/注射),或乙醇与这些药物或γ-羟基丁酸(GHB)(1.0或3.2毫克/千克/注射)的组合。每种药物或药物组合的反应要求在各实验阶段(10、32、100、320或1000)逐步增加。因变量为药物或药物组合维持的反应率以及当消费表示为价格函数时的药物需求弹性。
每种药物的弹性(P(最大值))值在猴子之间有所不同,但对猴子而言保持相同的排序顺序,表明动物对药物强化作用的明显敏感性存在根本差异。将乙醇与其他药物联合使用并未增加它们的强化效果。GHB(在先前研究中无效)并未改变乙醇的强化效果;乙醇与氟硝西泮组合的需求函数弹性略低于单独使用乙醇,但与单独使用氟硝西泮无异;向可卡因中添加乙醇会降低可卡因的强化效果。
乙醇与镇静和刺激药物联合使用是由于乙醇增强这些药物强化效果的能力这一假设未得到支持。