MECHANISMS OF OPIATE AND STIMULANT DRUG REINFORCEMENT

虽然这个项目开始只是为了调查 加强自我管理的药物的作用，我们的结果迄今为止， 确定了焦虑行为的存在， 影响动物穿越跑道的预强化行为， 静脉药物强化。 因此，建议进行实验， 进一步研究这两个对立的性质，程度和相互作用 自我管理药物的特性。 我们实验室开发的行为测试提供了一种方法 研究多巴胺（DA）的奖励衰减作用 拮抗剂药物在动物中，不再被麻醉时， 试验. 因此，这些试验得出的数据不受以下因素的混淆 神经抑制剂治疗的运动和镇静副作用。 我们 迄今为止的结果已经证实了DA在兴奋剂中的作用，而不是阿片类药物 加固. 建议进一步的实验来检查受体 抗精神病药"快感缺失"效应的特异性（D-1 vs D-2拮抗剂 研究），并使用 局部脑内灌注。 在静脉注射可卡因的实验中 强化，药物的意外致焦虑作用是 鉴定 这表现为安定可逆的"冲突" 在试验/天中逐渐增强的行为。 一系列 因此，建议进行研究，以a）评估这一普遍性 其他药物滥用和不同剂量药物之间的 可卡因;和B）确定造成这种现象的机制 通过比较各种药理学和 非药理学操作，以改变所观察到的 冲突行为 总之，这项研究的数据将提供 关于积极（加强）和消极方面的重要新信息 （焦虑）属性的自我管理的药物。 在这样做的工作， 对于阐明一些对立的观点有着明确的含义， 同时存在的因素共同决定了 人类的吸毒行为。

Although this project began solely as an investigation into the reinforcing actions of self-administered drugs, our results to date have identified the presence of anxiogenic actions that can dramatically affect the prereinforced behavior of animals traversing a runway for Intravenous drug reinforcement. Experiments are therefore proposed to further examine the nature, extent and interaction of these two opposing properties of self-administered drugs. Behavioral tests developed In our lab have provided a means of examining the putative reward-attenuating actions of dopamine (DA) antagonist drugs In animals that are no longer drugged at the time of testing. Data derived from these tests are not, therefore, confounded by the motoric and sedative side-effects of neuroleptic treatments. Our results thus far have confirmed a DA role in stimulant but not opiate reinforcement. Further experiments are proposed to examine the receptor specificity of neuroleptic "anhedonic" effects (D-1 vs D-2 antagonist studies) and to identify the drugs' central site(s) of action using localized Intracerebral infusions. In experiments with i.v. cocaine reinforcement, an unexpected anxiogenic action of the drug was identified. This took the form of a diazepam-reversible "conflict' behavior that grew progressively stronger across trials/days. A series of studies are therefore proposed to a) assess the generality of this phenomenon for other drugs of abuse and across different doses of cocaine; and b) identify the mechanisms responsible for this phenomenon by comparing the effectiveness of various pharmacological and nonpharmacological manipulations to alter the magnitude of the observed conflict behavior. Together, the data from this research will provide important new information on both the positive (reinforcing) and negative (anxiogenic) properties of self-administered drugs. In so doing the work has clear implications for elucidating some of the opposing yet concurrent factors that together determine the nature and extent of drug-taking behaviors in humans.