ROLE OF INSTRUMENTAL LEARNING IN TOLERANCE TO STIMULANTS

工具学习在兴奋剂耐受中的作用

• 批准号: 3210330
• 负责人: David Wolgin
• 金额: $ 7.88万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3210330
• 关键词: amphetamines; anorexic agent; apomorphine; chemical stimulation; cocaine; cues; discrimination learning; drug administration rate /duration; drug tolerance; haloperidol; injection /infusion; instinct; laboratory rat; methylphenidate; operant conditionings; psychological reinforcement; psychopharmacology; stimulus /response; suppression

The proposed research is designed to evaluate the hypothesis that contingent tolerance to the "anorexigenic" effect of amphetamine and related drugs involves learning to suppress incompatible responses. This hypothesis derives from the observation that such tolerance is accompanied by the suppression of stereotyped head scanning movements in bottle-fed, but not in cannula-fed, rats. To determine whether the suppression of stereotypy is under operant control, amphetamine-treated rats will be required to hold their heads stationary for intraoral mild infusions. Stimulus control will be assessed by making milk delivery contingent on suppression of stereotypy in the presence of a discriminiative cue. To determine whether prior sensitization of stereotypy retards tolerance development, rats will be given noncontingent injections of amphetamine prior to the tolerance phase. The generality of the hypothesis will be assessed by analyzing the effects of chronic injections of cocaine, methylphenidate, and apomorphine of the intake and activity of cannula- and bottle-fed rats. To determine whether tolerance occurs when motoric effects do not contribute to the suppression of intake, the effects of chronic pre- and post-test injections of amphetamine in cannula-fed rates will be compared. Finally, to determine whether contingent tolerance is suppressed when drug treatment blunts reinforcement, the effects of chronic pre- and post-test injections of haloperidol will be assessed. Taken together, the results of the proposed research will clarify the role of instrumental learning in drug tolerance and provide new insights into the relationship between tolerance and sensitization to stimulant drugs. This, in turn, may lead to new treatment strategies for extinguishing conditioned behaviors that contribute to stimulant drug abuse in humans.

这项拟议的研究旨在评估以下假设 对苯丙胺和安非他明的“厌食”效应的偶然性耐受性 相关药物包括学习抑制不相容的反应。这 假说源于这样的观察，即这种容忍是伴随着 通过抑制奶瓶喂养中刻板的头部扫描运动， 但不是在插管喂养的老鼠身上。以确定是否抑制 刻板印象在手术控制下，安非他明治疗的大鼠将 需要保持头部不动，以便进行口腔内温和输液。 刺激控制将通过使送奶视情况而定进行评估 在有歧视性提示的情况下抑制刻板印象。至 确定先前对刻板印象的敏感化是否会阻碍耐受性 在发育过程中，将给大鼠非偶然注射苯丙胺 在容忍阶段之前。该假设的一般性将是 通过分析长期注射可卡因的影响进行评估， 和阿朴吗啡对插管的摄入量和活性的影响--和 奶瓶喂养的老鼠。确定在驾驶汽车时是否出现耐受 影响并不有助于抑制摄取，影响 安非他明在试验前和试验后以插管喂食率进行慢性注射 将会被比较。最后，要确定或有容忍是否 抑制时药物治疗钝化强化，对慢性 将对测试前和测试后注射氟哌啶醇进行评估。已被占用 总而言之，拟议的研究结果将澄清 在药物耐受性方面的工具性学习，并提供对 刺激性药物耐受性与增敏的关系这, 反过来，可能导致新的治疗策略，以消除条件性 导致人类滥用兴奋剂的行为。