The proposed research is designed to evaluate the hypothesis that contingent tolerance to the """"""""anorexigenic"""""""" effect of amphetamine and related drugs involves learning to suppress incompatible responses. This hypothesis derives from the observation that such tolerance is accompanied by the suppression of stereotyped head scanning movements in bottle-fed, but not in cannula-fed, rats. To determine whether the suppression of stereotypy is under operant control, amphetamine-treated rats will be required to hold their heads stationary for intraoral mild infusions. Stimulus control will be assessed by making milk delivery contingent on suppression of stereotypy in the presence of a discriminiative cue. To determine whether prior sensitization of stereotypy retards tolerance development, rats will be given noncontingent injections of amphetamine prior to the tolerance phase. The generality of the hypothesis will be assessed by analyzing the effects of chronic injections of cocaine, methylphenidate, and apomorphine of the intake and activity of cannula- and bottle-fed rats. To determine whether tolerance occurs when motoric effects do not contribute to the suppression of intake, the effects of chronic pre- and post-test injections of amphetamine in cannula-fed rates will be compared. Finally, to determine whether contingent tolerance is suppressed when drug treatment blunts reinforcement, the effects of chronic pre- and post-test injections of haloperidol will be assessed. Taken together, the results of the proposed research will clarify the role of instrumental learning in drug tolerance and provide new insights into the relationship between tolerance and sensitization to stimulant drugs. This, in turn, may lead to new treatment strategies for extinguishing conditioned behaviors that contribute to stimulant drug abuse in humans.
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