Ginsburg Brett C, Lamb Richard J
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78228, USA.
Behav Pharmacol. 2006 May;17(3):249-57. doi: 10.1097/00008877-200605000-00006.
The cannabinoid CB1 antagonist rimonabant (SR141716A) has been proposed as a therapeutic agent for several addictive disorders, including alcoholism. Rimonabant may selectively reduce responding for an ethanol solution compared with an alternative. While this could represent a specific effect of CB1 inhibition on ethanol reinforcement, this could also result from differences in the baseline rates of behavior or experiences between comparison groups. We developed a procedure in rats that allows a within-subject comparison of ethanol and food-maintained responding and provides well matched baseline response rates. We determined the effects of acute doses of rimonabant (0.3-5.6 mg/kg, intraperitoneal) and the CB1 agonist Delta-9-tetrahydrocannabinol (1.0-5.6 mg/kg, intraperitoneal) on responding for food and ethanol under a multiple fixed-ratio schedule. To confirm that rimonabant blocked cannabinoid receptors, the ability of rimonabant to antagonize Delta-9-tetrahydrocannabinol effects in the same subjects under the same reinforcement schedule was also determined. In contrast with previous reports, rimonabant did not significantly alter responding for ethanol or food. The effects of Delta-9-tetrahydrocannabinol on responding for food were completely antagonized by rimonabant, whereas Delta-9-tetrahydrocannabinol effects on responding for ethanol were not. These results suggest that there may be neuroadaptation of the cannabinoid system following aging or chronic self-administration of ethanol.
大麻素CB1拮抗剂利莫那班（SR141716A）已被提议作为包括酒精中毒在内的几种成瘾性疾病的治疗药物。与另一种选择相比，利莫那班可能会选择性地减少对乙醇溶液的反应。虽然这可能代表CB1抑制对乙醇强化的特定作用，但这也可能是由于比较组之间行为或经历的基线率差异所致。我们在大鼠中开发了一种程序，该程序允许在个体内比较乙醇和食物维持的反应，并提供匹配良好的基线反应率。我们确定了急性剂量的利莫那班（0.3 - 5.6毫克/千克，腹腔注射）和CB1激动剂Δ9 - 四氢大麻酚（1.0 - 5.6毫克/千克，腹腔注射）在多重固定比率时间表下对食物和乙醇反应的影响。为了确认利莫那班阻断了大麻素受体，还确定了利莫那班在相同强化时间表下对同一受试者拮抗Δ9 - 四氢大麻酚作用的能力。与先前的报告相反，利莫那班并没有显著改变对乙醇或食物的反应。利莫那班完全拮抗了Δ9 - 四氢大麻酚对食物反应的影响，而Δ9 - 四氢大麻酚对乙醇反应的影响则没有被拮抗。这些结果表明，衰老或长期自我给药乙醇后，大麻素系统可能会发生神经适应性变化。
