Abuse of benzodiazepine/heroin combinations

描述（由申请人提供）： 苯二氮卓类药物与阿片类药物（如海洛因）的共同滥用是世界各地普遍存在的问题，因此有必要确定这种行为背后的机制。人类成瘾者声称，用苯二氮卓类药物预先治疗自己会加剧海洛因产生的快感。然而，没有足够的动物数据来支持或反对这一说法。本提案中概述的实验旨在通过检查苯二氮卓类/海洛因复方制剂在恒河猴中的相对强化有效性来解决这一问题，恒河猴接受了按照渐进比例给药方案自我给药海洛因的训练。此外，拟定的研究将通过给予对各种GABAA α亚基具有优先活性的苯二氮卓类激动剂（作为苯二氮卓类/海洛因复方制剂的一部分），研究介导这些行为效应的GABAA受体机制。总之，这些研究将确定动物愿意为这种药物组合工作的努力程度，以及GABAA受体的α 1和α 2亚基在多大程度上有助于这种行为？

DESCRIPTION (provided by applicant): Co-abuse of benzodiazepines with opiate drugs such as heroin is a prevalent problem throughout the world, making it necessary to identify the mechanism underlying this behavior. Human addicts claim that pre-treating themselves with benzodiazepines intensifies the high produced by heroin. However, there are not enough animal data to support or oppose this assertion. The experiments outlined in this proposal aim to address this issue by examining the relative reinforcing effectiveness of the benzodiazepine/heroin combination in rhesus monkeys trained to self-administer heroin on a progressive-ratio schedule of drug delivery. Additionally, the proposed studies will investigate GABAA receptor mechanisms mediating those behavioral effects by administering benzodiazepine agonists with preferential activity at various GABAA alpha subunits as part of the benzodiazepine/heroin combination. Together, these studies will determine how hard the animal is willing to work for this drug combination, and to what extent do the alpha 1 and alpha 2 subunits of the GABAA receptor contribute to this behavior?