INSTRUMENTAL LEARNING AND TOLERANCE TO STIMULANTS

描述：（申请人摘要） 根据定义，成瘾的特征是长期服用药物。 然而，关于兴奋剂药物的作用方式， 在慢性病中的行为。 拟议的长期目标 研究的目的是了解耐受性发展的机制， 这些药物的抑制作用。 我们的假设是 由两个连续过程介导：1）从厌食症中恢复，以及（2） 学习抑制刻板的动作，这会干扰进食。 这两个过程可以通过比较刺激剂的作用来分析 药物对插管和奶瓶喂养大鼠的乳汁摄入量的影响。 因为 刻板的动作不会干扰牛奶的摄入， 插管喂养的大鼠，喂养的抑制可以归因于 药物的副作用。 然而，在奶瓶喂养的大鼠中， 刻板印象有助于抑制进食。 的具体目标 本研究目的是：（1）证明厌食症的恢复是一种 学习抑制刻板动作的先决条件。 因此，宽容 应该从瓶状态转换到插管状态，但不 反之亦然 (2)为了确定是否耐受 服用兴奋剂的条件是在被麻醉的状态下能喝到牛奶。 （三） 探讨学习抑制刻板印象的边界条件 动作 不同剂量苯丙胺对大鼠脑皮层神经元功能的影响 大鼠保持固定的头部位置， 将研究口内输注乳汁。 (4)以确定是否 老鼠可以学会抑制可卡因引起的刻板动作 卡西酮和阿扑吗啡。 5)为了了解导致 瓶饲和（6）插管喂养大鼠耐受性的消散。 对破坏性行为的容忍度相对迅速的发展 兴奋剂的作用可能导致其广泛滥用。 到 行为容忍涉及工具学习的程度，建议 研究将为理解人们如何适应 这些药物的行为破坏作用。

DESCRIPTION: (Applicant's Abstract) By definition, addiction is characterized by chronic drug administration. Much remains to be learned, however, about the way stimulant drugs affect behavior under chronic conditions. The long-term objective of the proposed research is to understand the mechanisms by which tolerance develops to the hypophagic effect of these drugs. Our working hypothesis is that tolerance is mediated by two sequential processes: 1) recovery from anorexia and (2) learning to suppress stereotyped movements, which interfere with feeding. The two processes can be analyzed by comparing the effects of stimulant drugs on the milk intakes of cannula- and bottled-fed rats. Because stereotyped movements do not interfere with the ingestion of milk in cannula-fed rats, the suppression of feeding can be attributed to the anorexic effect of the drug. In bottle-fed rats, however, both anorexia and stereotypy contribute to the suppression of feeding. The specific aims of the project are: (1) To demonstrate that recovery from anorexia is a prerequisite to learning to suppress stereotyped movements. Thus, tolerance should transfer from the bottle condition to the cannula condition, but not vice versa. (2) To determine whether tolerance to the anorexic effects of stimulants is contingent on having access to milk in the drugged state. (3) To explore the boundary conditions for learning to suppress stereotyped movements. The effect of various doses of amphetamine on the ability of rats to maintain a stationary head position that is reinforced with intraoral milk infusions will be investigated. (4) To determine whether rats can learn to suppress stereotyped movements induced by cocaine cathinone, and apomorphine. 5) To understand the conditions responsible for the dissipation of tolerance in bottle- and (6) cannula-fed rats. The relatively rapid development of tolerance to the behaviorally disruptive effects of stimulant drugs may contribute to their widespread abuse. To the extent that behavioral tolerance involves instrument learning, the proposed research will provide a rationale for understanding how people adapt to the behaviorally disruptive effects of these drugs.