Department of Psychology, Idaho State University, Pocatello, ID 83209-8112, USA.
Exp Clin Psychopharmacol. 2011 Dec;19(6):389-400. doi: 10.1037/a0024142. Epub 2011 Jun 27.
Naloxone and rimonabant block neurotransmitter action of some drugs of abuse (such as ethanol, opiates, and nicotine), and thereby reduce drug seeking and self-administration by suppressing the drugs' reinforcing properties. The present study represents an attempt to elucidate whether these drugs may also reduce rewarding properties of other events, in this case, activity-based reinforcement. In Experiment 1, 10 obese and 10 lean Zucker rats pressed a locked door under a progressive ratio schedule of reinforcement that, when unlocked, provided access to a running wheel for 2-min intervals. After baseline breakpoints were established, doses of naloxone (0.3-10 mg/kg) were administered prior to experimental sessions. Obese rats exhibited lower baseline breakpoints for wheel activity, lower response rates, and fewer revolutions compared to lean rats. Naloxone decreased revolutions and response rates for lean and obese rats, but did not reduce breakpoints. In Experiment 2, five Long-Evans rats pressed a door to unlock a wheel for 20 s of wheel activity. Doses of rimonabant (1-10 mg/kg) were administered before some experimental sessions. The highest dose of rimonabant suppressed breakpoints and response rates, but did not affect revolutions. These data suggest that both drugs reduce the reinforcing properties of wheel running, but do so in different manners: naloxone may suppress wheel-based activity (consummatory behavior), but not seeking (appetitive behavior), and rimonabant does the converse. The data also support the role of endocannabinoids in the reinforcing properties of exercise, an implication that is important in terms of CB1 antagonists as a type of pharmacotherapy.
纳洛酮和利莫那班阻断某些滥用药物（如乙醇、阿片类药物和尼古丁）的神经递质作用，从而通过抑制药物的强化特性来减少药物的寻求和自我给药。本研究试图阐明这些药物是否也可以降低其他事件的奖赏特性，在这种情况下，是基于活动的强化。在实验 1 中，10 只肥胖和 10 只瘦 Zucker 大鼠在递增比例强化计划下按压上锁的门，当门解锁时，可进入运行轮进行 2 分钟的间隔。在建立基线断点后，在实验前给予纳洛酮（0.3-10mg/kg）的剂量。肥胖大鼠的轮活动基线断点较低，反应率较低，旋转次数较少。纳洛酮降低了肥胖和瘦大鼠的旋转次数和反应率，但没有降低断点。在实验 2 中，5 只 Long-Evans 大鼠按压一扇门，解锁轮子，进行 20 秒的轮子活动。在一些实验前给予利莫那班（1-10mg/kg）的剂量。最高剂量的利莫那班抑制了断点和反应率，但不影响旋转次数。这些数据表明，两种药物都降低了轮子运动的强化特性，但方式不同：纳洛酮可能抑制基于轮子的活动（消耗性行为），而不是寻求（食欲行为），而利莫那班则相反。这些数据还支持内源性大麻素在运动强化特性中的作用，这对于作为一种药物治疗的 CB1 拮抗剂具有重要意义。
