Drug and reinforcement history as determinants of the response-maintaining effects of quinpirole in the rat
Drug and reinforcement history as determinants of the response-maintaining effects of quinpirole in the rat
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DOI：
10.1124/jpet.107.123042
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发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Woods, James H.
中科院分区：
文献类型：
--
作者：
Collins, Gregory T.;Woods, James H.
本研究考察了药物和强化史对大鼠喹匹罗维持反应的影响。喹匹罗（0.01、0.032或0.1 mg/kg每次注射）被评估为实验初始大鼠的强化剂，以及在固定比例1的强化计划下训练自我管理可卡因、瑞芬太尼、氯胺酮或食物的大鼠。昆匹罗在实验初期的大鼠，或氯胺酮或食物训练的大鼠中未能保持反应。然而，在有可卡因强化史的大鼠中保持了强劲的反应，而在有瑞芬太尼强化史的大鼠中观察到适度的反应水平。在第二组研究中，评估了长期用药史对食物训练大鼠喹匹罗维持反应的影响。通过食物强化维持大鼠，然后允许不同组的大鼠对生理盐水、喹匹罗和反应性可卡因有反应或给予非反应性可卡因；随后让所有大鼠对喹匹罗有反应。只有先前对可卡因有反应的大鼠表现出喹匹罗维持的反应；所有其他条件均未能建立喹匹罗维持应答。虽然当用喹匹罗替代可卡因时观察到的高水平的喹匹罗维持反应提示了积极的强化作用，但这些维持反应的作用高度依赖于药物和强化史，这表明喹匹罗可能只在非常特定的条件下起强化作用。在这些情况下，与其他药物强化剂相比，喹匹罗的行为效应代表了一种新的行为组合，它们表明，自我给药喹匹罗的直接效应可能是建立反应维持效应的重要因素。
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.