MECHANISMS OF OPIATE AND STIMULANT DRUG REINFORCEMENT

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Although this project began solely as an investigation into the reinforcing actions of self-administered drugs, our results to date have identified the presence of anxiogenic actions that can dramatically affect the prereinforced behavior of animals traversing a runway for Intravenous drug reinforcement. Experiments are therefore proposed to further examine the nature, extent and interaction of these two opposing properties of self-administered drugs. Behavioral tests developed In our lab have provided a means of examining the putative reward-attenuating actions of dopamine (DA) antagonist drugs In animals that are no longer drugged at the time of testing. Data derived from these tests are not, therefore, confounded by the motoric and sedative side-effects of neuroleptic treatments. Our results thus far have confirmed a DA role in stimulant but not opiate reinforcement. Further experiments are proposed to examine the receptor specificity of neuroleptic "anhedonic" effects (D-1 vs D-2 antagonist studies) and to identify the drugs' central site(s) of action using localized Intracerebral infusions. In experiments with i.v. cocaine reinforcement, an unexpected anxiogenic action of the drug was identified. This took the form of a diazepam-reversible "conflict' behavior that grew progressively stronger across trials/days. A series of studies are therefore proposed to a) assess the generality of this phenomenon for other drugs of abuse and across different doses of cocaine; and b) identify the mechanisms responsible for this phenomenon by comparing the effectiveness of various pharmacological and nonpharmacological manipulations to alter the magnitude of the observed conflict behavior. Together, the data from this research will provide important new information on both the positive (reinforcing) and negative (anxiogenic) properties of self-administered drugs. In so doing the work has clear implications for elucidating some of the opposing yet concurrent factors that together determine the nature and extent of drug-taking behaviors in humans.