Abuse of benzodiazepine/heroin combinations

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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?