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Method: To evaluate this hypothesis, rhesus monkeys were trained to self-administer intravenous (i.v.) injections of either midazolam (a short-acting benzodiazepine with non-selective agonist efficacy at alpha1, 2, 3 and 5 subunit-containing GABAA receptors) or cocaine (monoamine uptake blocker) under a progressive-ratio schedule, in which response requirements doubled during the course of a session. We evaluated the reinforcing effects of classical benzodiazepines, midazolam and lorazepam, as well as MRK-696 which has weak partial agonist efficacy at each of the four subtypes. Three alpha1-sparing compounds were evaluated: TPA023B and MRK-623 (zero intrinsic efficacy at alpha1, partial agonist at alpha2, 3, and 5), and TP003 (zero efficacy at alpha1, low partial agonist efficacy at alpha2 and alpha5, full efficacy at alpha3).

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Methods: To evaluate this hypothesis, rhesus monkeys were trained to self-administer intravenous (i.v.) injections of either midazolam (a short-acting benzodiazepine with non-selective agonist efficacy at alpha1, 2, 3 and 5 subunit-containing GABAA receptors) or cocaine (monoamine uptake blocker) under a progressive-ratio schedule, in which response requirements doubled during the course of a session. 84d34552a1