MECHANISMS OF OPIATE AND STIMULANT DRUG REINFORCEMENT

阿片类药物和兴奋剂药物的强化机制

• 批准号: 3211017
• 负责人: AARON ETTENBERG
• 金额: $ 10.97万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211017
• 关键词: amphetamines; antipsychotic agents; behavior test; behavioral extinction; benzodiazepines; buspirone; carbamazepine; central nervous system stimulants; clonazepam; clonidine; cocaine; dopamine; dopamine receptor; haloperidol; heroin; laboratory rat; morphine; operant conditionings; opiate alkaloid; phenobarbital; pimozide; psychomotor function; psychopharmacology; receptor binding; reinforcer

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.

尽管这个项目最初只是为了调查 加强自我管理药物的作用，我们迄今为止的结果 确定了致焦虑作用的存在，可以显着 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 进一步研究这两种对立的性质、程度和相互作用 自行给药药物的特性。 我们实验室开发的行为测试提供了一种方法 检查多巴胺 (DA) 的假定奖赏衰减作用 拮抗剂药物 在动物中不再服用药物 测试。 因此，从这些测试中得出的数据不会与 抗精神病药治疗的运动和镇静副作用。 我们的 迄今为止的结果已证实 DA 在兴奋剂中发挥作用，但在阿片类药物中没有作用 加强。 提出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 与 D-2 拮抗剂 研究）并使用以下方法确定药物的中心作用位点： 局部脑内输注。 在静脉注射实验中可卡因 强化，药物的意外致焦虑作用是 确定。 这采取了地西泮可逆“冲突”的形式 在试验/几天中逐渐增强的行为。 A系列 因此，建议进行多项研究 a) 评估该研究的普遍性 其他药物滥用和不同剂量的现象 可卡因; b) 确定造成这种现象的机制 通过比较各种药理作用和效果 非药物操作来改变观察到的程度 冲突行为。 这项研究的数据将共同提供 关于积极（强化）和消极的重要新信息 自行给药药物的（致焦虑）特性。 在这样做的过程中 对于阐明一些反对意见具有明显的意义 共同决定的性质和程度的并发因素 人类的吸毒行为。