ANXIOLYTICS AS DISCRIMINATIVE STIMULI

因为苯二氮卓类（BZ）和其他抗焦虑药是最常见的 所有药物的广泛处方，抗焦虑药的误用，滥用， 生理依赖性和长期使用的行为后遗症， 持续关注。 在了解结构和 BZ/GABA-受体复合物的功能导致了新的 被认为作为抗焦虑药或催眠药更具选择性的化合物， 不太可能导致滥用和生理依赖。 药物 在实验室动物中的区分（DD）程序提供了高度的 CNS活动的选择性行为测量，通常是 其特征在于类似于关于主观药物作用的信息 在人类中，据推测， 自我管理，药物的强化和辨别刺激 影响是共同的。 DD范式在以下方面很有前途： 提供了对相当多的人之间的对应程度的独特见解 特定行为效应和药物在特定 神经递质系统 该项目的一个主要目标是探索 系统地分析了歧视性的 药物的刺激和强化作用。 有人认为， 某些药物历史可以增加自我管理的可能性， 其他精神活性化合物，实验将研究药物 自我管理方面的歧视以及 关于随后自我给药的药物歧视培训的历史 且反之亦然。 该项目的第二个主要目标是研究 不仅抗焦虑药物本身的一般化概况，而且作为 以前和同时进行的辨别训练的功能 毒品 第三个主要目标是研究辨别刺激 抗焦虑药在长期服用BZ之前、期间和之后的作用 特别是在多大程度上， 或多或少对药物的辨别刺激效应敏感。 第四 主要目的是研究在何种程度上的分子机制， 抗焦虑药和具有特异性活性的化合物的作用 γ-氨基丁酸（GABA）/BZ-受体复合物对应于它们的 区别性刺激效应。 实验将探索中央 GABA/BZ-受体的辨别性刺激效应的介导 配体和新的推定的刺激效应的区别 抗焦虑药和其它在抗抑郁药中显示相对特异活性的化合物， 这个受体复合物。

Because benzodiazepines (BZ) and other anxiolytics are among the most widely prescribed of all medications, anxiolytic misuse, abuse, physiological dependence, and behavioral sequelae of long-term use are of continuing concern. Recent advances in understanding the structure and function of the BZ/GABA-receptor complex have led to development of novel compounds believed to be more selective as anxiolytics or hypnotics and less likely to lead to abuse and physiological dependence. Drug discrimination (DD) procedures in laboratory animals provide highly selective behavioral measures of CNS activity, which often are characterized as being analogous to information on subjective drug effects in humans, and it has been speculated that, with drugs that are self-administered, the drug's reinforcing and discriminative stimulus effects are coextensive. The DD paradigm is promising in its ability to provide unique insight into the degree of correspondence between a rather specific behavioral effect and that drug's activity in a specific neurotransmitter system. One major objective of the project is to explore systematically the possible interrelationships between the discriminative stimulus and reinforcing effects of drugs. There is some suggestion that certain drug histories can increase the probability of self-administering other psychoactive compounds, and experiments will study drug discrimination in the context of self-administration and the effects of histories of drug discrimination training on subsequent self-administration and vice versa. A second major objective of the project is to study not only the generalization profiles for anxiolytic drugs per se but also as a function of previous and concurrent discrimination training with other drugs. A third major objective is to study the discriminative stimulus effects of anxiolytics before, during, and after chronic BZ administration to address specifically the extent to which post-dependent subjects may be more or less sensitive to drug discriminative-stimulus effects. A fourth major objective is to study the extent to which molecular mechanisms of action of anxiolytics and compounds with specific activity at the gamma-aminobutyric acid (GABA)/BZ-receptor complex correspond to their discriminative stimulus effects. Experiments will explore central mediation of the discriminative stimulus effects of GABA/BZ-receptor ligands and the discriminative stimulus effects of novel putative anxiolytics and other compounds showing relatively specific activity in this receptor complex.