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Amphetamine sensitization disrupts certain aspects of associative learning about natural rewards Cantor, Anna

Abstract

Repeated exposure to psychostimulant drugs induces numerous behavioral, and neuronal changes, which in animals is thought to model certain neural adaptations that may contribute to drug addiction. Chronic AMPH has repeatedly been shown to alter the acquisition and expression of associations between a conditioned stimulus (CS) and natural rewards. Although repeated psychostimulant exposure can interfere with associative learning about natural food rewards, the manner in which these treatments affect acquisition and expression of these associations remains unclear. The current study investigated how repeated AMPH exposure (5 x 2 mg/kg over 10 days) affects learning, extinction and cue-induced reinstatement of instrumental responding of food-seeking behavior. Rats were trained over 7 days to press one of two levers for food and a tone/light CS. During subsequent extinction conducted over 3-6 days, responding delivered neither food nor the CS. On reinstatement tests, active lever presses produced the CS, but not food. Rats received repeated AMPH or saline prior to training (exp. 1A), after instrumental training (exp. 1B), or after training and extinction (exp. 1C). In experiment 1A, cue-induced reinstatement was blunted significantly in AMPH-treated rats. In contrast, AMPH-treatment after initial training (experiment 1B) significantly retarded extinction relative to controls, but did not affect cue-induced reinstatement. In experiment 1C, AMPH exposed rats displayed enhanced cue-induced reinstatement. Experiment 2 was conducted to clarify the results of experiment 1A. Rats were trained to nosepoke for food following a CS, and were then tested in the presence of two novel levers, responding on one delivered the food-associated CS. AMPH treatment impaired the acquisition of a new response with conditioned reinforcement. These findings suggest that repeated AMPH exposure prior to formation of response-CS associations selectively disrupts the ability of food-related stimuli to influence instrumental responding. Exposure after initial associative learning impedes extinction. AMPH administration after training and extinction enhance responding. Collectively, these findings suggest that AMPH sensitization can perturb certain aspects of amygdala-mediated associative learning related to natural, food rewards, and this impairment seems to reflect a weakened CS-reward association as opposed to a reduced preference for the food.

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Attribution-NoDerivs 2.5 Canada

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