STUDY OF STIMULANT-INDUCED CONDITIONED DRUG EFFECTS

巴甫洛夫条件性药物效应对关键药物的重要贡献 滥用治疗复发和渴求的问题。条件反射的应用 然而，治疗的原则是复杂的，因为药物 影响可以根据各种各样的外部感觉环境而定 与吸毒和戒毒程序有关的刺激只能 抑制但不能消除条件刺激(CS)的效果 诱导条件性反应(CR)。在这方面，它是 在物种灭绝后的条件效应测试中得到了很好的证实 无论是药物模型还是非药物模型，CS都可以诱导CR 在惊吓和压力刺激下恢复状态。最近我们发现， 咖啡因还可以重新激活一种已熄灭的条件性多巴胺能 药物反应。咖啡因对脑内CS效应的调节作用 药物调节很重要，因为它创造了 发展神经化学机制的药理学特性 调节条件性药物效应。因此，当前的一个目标是 建议将咖啡因对药物的调节影响联系起来 咖啡因机制的条件化过程；例如腺苷 拮抗、去甲肾上腺素释放和GABA能拮抗。另一个 目的探讨非处方药对兴奋剂的影响。 (即甲基黄嘌呤和苯乙胺)对一种 条件性多巴胺能药物反应消失。总体而言，目标是 就是识别，用单侧6-羟基多巴胺旋转和放置 偏爱动物模型，可促进/拮抗的药物治疗 CS对多巴胺能药物诱导的条件性药物反应的疗效 滥用倾向高的药物，如苯丙胺、可卡因和 吗啡。所得结果可为药理研究提供依据。 临床控制渴求及伴随复发的治疗策略 药物滥用康复过程中存在的问题。

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.