A STUDY OF STIMULANT-INDUCED CONDITIONED DRUG EFFECTS

巴甫洛夫条件性药物效应对关键药物 滥用治疗问题的复发和渴望。条件作用的应用 然而，治疗原则是复杂的，因为药物 影响可以调节到各种各样的外感受性环境 与吸毒有关的刺激和消除程序只能 抑制但不能消除条件刺激（CS）的功效 条件反应（CR）。在这方面 在灭绝后的条件效应测试中得到了很好的确立， 在药物和非药物模型中，CR的CS诱发可以是 通过惊吓和压力刺激恢复。最近，我们发现， 咖啡因也可以重新激活一个熄灭的条件多巴胺能神经元， 药物反应咖啡因与CS功效的调节的这种联系， 药物调节很重要，因为它创造了 开发神经化学机制的药理学特性， 调节条件性药物作用。因此，本发明的一个目的是 建议将咖啡因对药物的调节作用 调节咖啡因机制的过程;例如腺苷 拮抗、去甲肾上腺素释放和GABA能拮抗。另一 目的是检查非处方兴奋剂药物的影响 (i.e.,甲基黄嘌呤和苯乙胺）对一个 消除条件性多巴胺能药物反应。总体而言，目标 是用单侧6-羟基多巴胺旋转并放置 偏好动物模型，可以促进/拮抗 多巴胺能药物诱导的条件性药物反应中的CS-功效和 滥用倾向高的药物，如安非他明、可卡因和 吗啡所得结果可为药理学研究提供依据 临床控制渴望和伴随的复发的治疗策略 戒毒康复期间的问题。

Pavlovian conditioned drug effects contribute importantly to critical drug abuse treatment issues of relapse and craving. Application of conditioning principles to treatment are complicated, however, by the fact that drug effects can be conditioned to a wide variety of exteroceptive environmental stimuli associated with drug use and that extinction procedures can only suppress but cannot eliminate the efficacy of the conditioned stimulus (CS) to elicit the conditioned response (CR). In this regard, it is well-established by tests of conditioned effects following extinction in both drug and non-drug models, that CS elicitation of the CR can be reinstated by startle and stress stimuli. Recently, we have found that caffeine could also reactivate an extinguished conditioned dopaminergic drug response. This linkage of caffeine to the modulation of CS efficacy in drug conditioning is important because it creates the possibility of developing a pharmacological identity of the neurochemical mechanisms which modulate conditioned drug effects. Thus, one objective of the present proposal is to relate the modulatory influence of caffeine on drug conditioning processes to caffeine mechanisms; e.g. to adenosine antagonism, norepinephrine release and GABAergic antagonism. Another objective is to examine the influence of over-the counter stimulant drugs (i.e., methylxanthines and phenylethylamines) on the reactivation of an extinguished conditioned dopaminergic drug response. Overall, the objective is to identify, using the unilateral 6-hydroxydopamine rotation and place preference animal models, drug treatments which can facilitate/antagonize CS-efficacy in conditioned drug responses induced by dopaminergic drugs and by drugs with high abuse liability such as amphetamine, cocaine and morphine. The results obtained can provide a basis for pharmacological treatment strategies for clinical control of craving and attendant relapse problems during drug abuse rehabilitation.