By definition, addiction is characterized by chronic drug administration. Much remains to be learned, however, about the way stimulant drugs affect behavior under chronic conditions. The long-term objective of the proposed research is to understand the mechanisms by which tolerance develops to the hypophagic effect of these drugs. Our working hypothesis is that tolerance is mediated by two sequential processes: 1) recovery from anorexia and (2) learning to suppress stereotyped movements, which interfere with feeding. The two processes can be analyzed by comparing the effects of stimulant drugs on the milk intakes of cannula- and bottled-fed rats. Because stereotyped movements do not interfere with the ingestion of milk in cannula-fed rats, the suppression of feeding can be attributed to the anorexic effect of the drug. In bottle-fed rats, however, both anorexia and stereotypy contribute to the suppression of feeding.
The specific aims of the project are: (1) To demonstrate that recovery from anorexia is a prerequisite to learning to suppress stereotyped movements. Thus, tolerance should transfer from the bottle condition to the cannula condition, but not vice versa. (2) To determine whether tolerance to the anorexic effects of stimulants is contingent on having access to milk in the drugged state. (3) To explore the boundary conditions for learning to suppress stereotyped movements. The effect of various doses of amphetamine on the ability of rats to maintain a stationary head position that is reinforced with intraoral milk infusions will be investigated. (4) To determine whether rats can learn to suppress stereotyped movements induced by cocaine cathinone, and apomorphine. 5) To understand the conditions responsible for the dissipation of tolerance in bottle- and (6) cannula-fed rats. The relatively rapid development of tolerance to the behaviorally disruptive effects of stimulant drugs may contribute to their widespread abuse. To the extent that behavioral tolerance involves instrument learning, the proposed research will provide a rationale for understanding how people adapt to the behaviorally disruptive effects of these drugs.
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