This proposal focuses on evaluation of the reinforcing effects of two classes of drug. One is the benzodiazepine (BZ) ligands that act on BZ receptors or on a subtype of these receptors, either as high or low efficacy agonists. The second class is defined both chemically and pharmacologically. Chemically, these drugs are phenylisopropylamine derivatives. Pharmacologically, they are either stimulants such as amphetamine, entactogens such as MDMA and MDA, or hallucinogens such as DOM Also, current projects evaluating the reinforcing effects of stimulant and depressant drugs that are submitted by industry, academia, and governmental agencies will continue. The procedures to study these compounds involve their contingent intravenous administration by rhesus monkeys under an FR10 TO 10"""""""" schedule of drug delivery. The baseline drug is 0.1 mg/kg methohexital, and the test compounds will be substituted on this baseline. In particularly interesting cases, i.e., if a low efficacy BZ agonist maintains similar rates of responding as a higher efficacy BZ agonist, the FR contingency will be increased systematically to determine if the biochemically- determined differences in efficacy are reflected in a different capacity to maintain responding in the face of increased FR requirements. in addition to this evaluation, this project will initiate studies that are designed to determine whether the endocrinological responses to drugs of abuse are the same in animals that actively self-administer drugs as is those that receive the same doses by passive administration. For this research, pairs of rhesus monkeys will be yoked in experiments in which the drug self-administered by one animal is received as well by its partner. Blood will be drawn from both animals through the indwelling catheters at appropriate times during this study and analyzed by Dr. Cicero for endocrinological changes. The roles of the animals will be switched -- the passive monkey becomes active and vice versa -- and the importance of control of the administration of the drug should be ascertained.
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