MECHANISMS OF OPIATE AND STIMULANT DRUG REINFORCEMENT

虽然这个项目开始时只是为了调查 加强自我给药的作用，我们到目前为止的结果是 确定了焦虑行为的存在，这些行为可以显著地 影响动物在跑道上的强制行为 静脉注射药物强化。因此，建议进行实验，以 进一步考察这两个对立的性质、范围和相互作用 自我给药的性质。 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)可能的奖赏减弱作用 动物体内不再下药的拮抗剂药物 测试。因此，从这些测试中得出的数据不会受到 抗精神病药治疗的运动和镇静副作用。我们的 到目前为止，结果证实了DA在兴奋剂中的作用，但不是阿片类药物 增援。建议进行进一步的实验来检测该受体。 抗精神病药“无快感”作用的特异性(D-1与D-2拮抗剂 研究)，并确定药物的中心部位(S)的作用 局部脑内输液。在静脉注射的实验中。可卡因 强化，一个意想不到的焦虑作用的药物是 已确认身份。这以安定可逆的“冲突”的形式出现 在试验/日子里逐渐变得更强的行为。一系列 因此，建议进行多项研究，以a)评估这方面的一般性 滥用其他药物的现象以及跨越不同剂量的 可卡因；以及b)查明造成这一现象的机制 通过比较不同药物和药物的有效性 非药物操作以改变观察到的 冲突行为。总而言之，这项研究的数据将提供 关于正面(强化)和负面的重要新信息 (引起焦虑的)自我给药的特性。在这样做的过程中 对澄清一些反对的观点有明显的影响 共同决定的共同因素的性质和程度 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.