The Discriminative Stimulus Properties of the kappa Opioid, U-50,488H in Rats
Minard, Veronica S.
The discriminative stimulus effects of the K-opioid antagonist, U-50,488H, were examined in this study. During training sessions, rats were conditioned to discriminate U-50, 488H versus vehicle (saline). Five male rats were food deprived to 85% of their free-feeding weight. They were then trained to respond with discriminatory lever pressing under a fixed-ratio 20 (FR 20) schedule of food presentation for 20 minutes. The training session began after a 10 minute pre-session following the injection of either drug or vehicle. Vehicle responding acted as a control for response rates (responses/sec) in this study. After reaching certain predetermined criteria, three of the rats were then used in generalization testing. This testing was identical to that of the training sessions except that varying doses ofU-50,488H were substituted for the training dose (10.0 mg/kg) and responding on both levers was reinforced. The drug studied, U-50,488H, produced dose-related decreases in the rate of responding. The administration of a low dose of drug resulted in a loss of discrimination between saline and drug in two of the rats studied. These results indicate that U-50,488H can be used as a discriminative stimulus in operant conditioning paradigms. The use of discrimination paradigms allows the observer to examine the subjective effects of a drug, in the case of U-50,488H, the subjective dysphoric effects that are produced. The future implications of this study are to discover a drug that, when administered in conjunction with U-50,488H, could antagonize the dysphoric effects associated with U-50,488H. Removing these aversive side effects could allow for the clinical implementation of this drug as a powerful analgesic.
iv, 22 p.
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