Rasmussen Erin B, Huskinson Sally L
Department of Psychology, Idaho State University, Idaho, USA.
Behav Pharmacol. 2008 Oct;19(7):735-42. doi: 10.1097/FBP.0b013e3283123cc2.
This experiment reports on the ability of rimonabant to alter the reinforcing properties of food in the genetically obese Zucker (fa/fa) rat, a strain that exhibits higher levels of endocannabinoids in brain regions that correspond to heightened food intake. We characterized food reinforcement in obese and lean Zucker rats by placing behavior under progressive ratio schedules of sucrose reinforcement. Then, doses of rimonabant (1-10 mg/kg), a CB1 receptor antagonist, were administered. Obese Zuckers had slightly higher breakpoints for sucrose under baseline conditions compared with leans, and also demonstrated significantly higher response rates than leans. Rimonabant dose-dependently decreased breakpoints and response rates for both groups, though only obese Zuckers demonstrated suppressed behavior under the 1 mg/kg dose. The 10 mg/kg dose of rimonabant reduced breakpoints equally for both groups (by about 60%). This dose of rimonabant also reduced food intake by 20% in lean Zuckers, and by 30% in obese Zuckers. These findings extend the literature that rimonabant reduces food reinforcer efficacy, and suggest that obese Zuckers may exhibit a heightened sensitivity to rimonabant. The findings also suggest that the effort required to obtain food reinforcement may also play a role in the efficacy of rimonabant.
本实验报告了利莫那班改变遗传性肥胖的 Zucker（fa/fa）大鼠食物强化特性的能力，该品系在与食物摄入量增加相对应的脑区中内源性大麻素水平较高。我们通过将行为置于蔗糖强化的累进比率程序下，对肥胖和瘦 Zucker 大鼠的食物强化进行了表征。然后，给予 CB1 受体拮抗剂利莫那班（1 - 10 mg/kg）剂量。与瘦 Zucker 大鼠相比，肥胖 Zucker 大鼠在基线条件下对蔗糖的断点略高，并且反应率也显著高于瘦 Zucker 大鼠。利莫那班剂量依赖性地降低了两组的断点和反应率，不过只有肥胖 Zucker 大鼠在 1 mg/kg 剂量下表现出行为抑制。10 mg/kg 剂量的利莫那班使两组的断点同等程度降低（约 60%）。该剂量的利莫那班还使瘦 Zucker 大鼠的食物摄入量减少了 20%，肥胖 Zucker 大鼠减少了 30%。这些发现扩展了关于利莫那班降低食物强化效果的文献，并表明肥胖 Zucker 大鼠可能对利莫那班表现出更高的敏感性。这些发现还表明，获得食物强化所需的努力可能也在利莫那班的疗效中起作用。
