ROLE OF INSTRUMENTAL LEARNING IN TOLERANCE TO STIMULANTS

拟议的研究旨在评估假设， 对安非他明的“致毒”作用的偶然耐受， 相关药物包括学习抑制不相容的反应。 这 一个假设来自这样的观察，即这种宽容是伴随着 通过在瓶喂中抑制定型的头部扫描运动， 但在插管喂养的大鼠中没有。 以确定是否抑制 刻板性是在操作控制下，安非他明治疗的大鼠将 需要保持头部固定以进行口内轻度输液。 刺激控制将通过使牛奶供应取决于 在存在区分性线索的情况下抑制刻板印象。 到 确定先前对刻板印象的敏感性是否会延迟耐受性 发展，大鼠将给予非偶然注射安非他明 在宽容期之前。 假设的一般性将是 通过分析长期注射可卡因的影响来评估， 哌甲酯，阿扑吗啡的摄入量和活动的套管-和 奶瓶喂养的老鼠 为了确定运动时是否出现耐受性， 影响并不有助于抑制摄入， 在插管喂养率中慢性试验前后注射安非他明 将被比较。 最后，为了确定偶然公差是否 当药物治疗减弱强化时，慢性 将评估氟哌啶醇的试验前和试验后注射。 采取 总之，拟议研究的结果将澄清以下方面的作用： 工具学习在药物耐受性，并提供新的见解， 对兴奋剂药物的耐受性和敏感性之间的关系。 这个， 反过来，可能导致新的治疗策略， 导致人类滥用兴奋剂的行为。

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.