The acquisition of the reinforcing effects of drugs will be studied in rhesus monkeys. Initially, orally delivered ethanol will be established as a reinforcer. Other drugs will be established as reinforcers by a procedure originally used in transfer of discriminative control from one stimulus to another. This procedure will be applied to the transfer of control from the reinforcing effects of ethanol to the reinforcing effects of other drugs such as cocaine, etonitazene, and pentobarbital. The drug under study will be gradually added to an ethanol solution that is available to monkeys under a VR 16 schedule. Then the ethanol concentration will gradually decreased to zero. In preliminary studies this procedure resulted in the rapid and reliable establishment of the new drug as a reinforcer. Probes with the new drug will be inserted at various points in the acquisition procedure to monitor the development of control by the reinforcing effects of the new drug. In addition an initial 30 min component, in which drug intake will not occur, will precede access to the component with drug availability; access to the component with drug will be contingent upon responding in the first component. Thus, responding in this initial 30 min component will reflect the reinforcing adequacy of the drug or drug combination in the second component without being disrupted by direct drug effects. The effects of experimental history on the acquisition of reinforcing effects will be assessed by comparing two groups of monkeys that differ in the sequence in which different drugs have been established as reinforcers. A relatively large number of monkeys (n=16) will be studied. Thus it will be possible to assess the generality of findings and to describe individuals differences in drug reinforced behavior. Additionally, it will be possible to determine if rapid development of control by the reinforcing effects of one drug, such as cocaine, correlates with the rapid development of control by the reinforcing effects of another drug, such as pentobarbital.
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