Collins Gregory T, Woods James H
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0632, USA.
J Pharmacol Exp Ther. 2007 Nov;323(2):599-605. doi: 10.1124/jpet.107.123042. Epub 2007 Aug 3.
The present study examined the effect of drug and reinforcement history on quinpirole-maintained responding in rats. Quinpirole (0.01, 0.032, or 0.1 mg/kg per injection) was assessed as a reinforcer in experimentally naive rats, as well as in rats trained to self-administer cocaine, remifentanil, ketamine, or food under a fixed ratio 1 schedule of reinforcement. Quinpirole failed to maintain responding in experimentally naive rats, or in ketamine- or food-trained rats. However, robust responding was maintained in rats with a history of cocaine reinforcement, and modest levels of responding were observed in rats with a history of responding for remifentanil. In a second set of studies, the effects of protracted drug histories on quinpirole-maintained responding in food-trained rats were assessed. Rats were maintained with food reinforcement, and different groups of rats were then allowed to respond for saline, quinpirole, and response-contingent cocaine or were administered noncontingent cocaine; all rats were subsequently allowed to respond for quinpirole. Only rats that previously responded for cocaine showed quinpirole-maintained responding; all other conditions failed to establish quinpirole-maintained responding. Although the high levels of quinpirole-maintained responding observed when quinpirole was substituted for cocaine are suggestive of positive reinforcing effects, these response-maintaining effects were highly dependent upon both drug and reinforcement history, suggesting that quinpirole may only function as a reinforcer under very specific conditions. The behavioral effects of quinpirole under these situations represent a novel constellation of actions relative to other drug reinforcers, and they suggest that the direct effects of self-administered quinpirole may be important in establishing the response-maintaining effects.
本研究考察了药物和强化史对大鼠喹吡罗维持反应的影响。将喹吡罗(每次注射0.01、0.032或0.1mg/kg)作为强化物,在未经实验的大鼠以及经训练在固定比率1强化程序下自我给药可卡因、瑞芬太尼、氯胺酮或食物的大鼠中进行评估。喹吡罗未能在未经实验的大鼠、氯胺酮训练的大鼠或食物训练的大鼠中维持反应。然而,有可卡因强化史的大鼠维持了强烈的反应,对瑞芬太尼有反应史的大鼠观察到适度的反应水平。在第二组研究中,评估了长期药物史对食物训练大鼠中喹吡罗维持反应的影响。大鼠通过食物强化维持,然后不同组的大鼠被允许对生理盐水、喹吡罗以及反应性可卡因做出反应或给予非反应性可卡因;随后所有大鼠被允许对喹吡罗做出反应。只有先前对可卡因有反应的大鼠表现出喹吡罗维持的反应;所有其他条件均未能建立喹吡罗维持的反应。尽管当用喹吡罗替代可卡因时观察到高水平的喹吡罗维持反应提示有正性强化作用,但这些反应维持作用高度依赖于药物和强化史,这表明喹吡罗可能仅在非常特定的条件下起强化物的作用。在这些情况下喹吡罗的行为效应代表了相对于其他药物强化物的一组新的作用,并且它们表明自我给药喹吡罗的直接效应可能对建立反应维持效应很重要。