Formation and Maintenance of Appetitive Pavlovian Associations
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Formation and Maintenance of Appetitive Pavlovian Associations

Abstract

Environmental stimuli associated with a drug or natural reward have the ability to elicit strong cravings and relapse bouts in human addicts and individuals with addiction-related psychopathologies such as compulsive eating disorders. In order for these environmental stimuli to drive reward-seeking behavior, however, Pavlovian associations between the environmental stimuli and the reward must first be acquired, and the memory of those associations must be successfully maintained. This aim of this dissertation is to investigate the mechanisms underlying the formation and maintenance of such appetitive Pavlovian associations, using two models of appetitive Pavlovian conditioning: morphine conditioned place preference (mCPP) and Pavlovian conditioned approach (PCA).

The first set of experiments described in this dissertation investigated the ability of the psychostimulant amphetamine (AMPH) to modulate the consolidation and reconsolidation of mCPP. These experiments found that AMPH injected immediately after training and memory reactivation enhanced mCPP. The second set of experiments investigated the effect of AMPH and the protein synthesis inhibitor anisomycin (ANI) on the consolidation and reconsolidation of PCA. Both AMPH and ANI modulated PCA behavior when injected immediately after training, but not when injected after memory reactivation. The third set of experiments used reversible inactivation as well as infusions of ANI to investigate the role of the nucleus accumbens (NAcc) core and shell in the consolidation and expression of PCA and cued fear conditioning, a form of aversive Pavlovian conditioning. These experiments showed that the NAcc core (but not the shell) is involved in the consolidation, but not the expression, of cued fear conditioning. In contrast, both NAcc subnuclei were necessary for the expression, but not the consolidation, of PCA.

These findings collectively demonstrate that the consolidation of mCPP and PCA can be modulated in a manner similar to other types of learning and memory, that a drug of abuse such as AMPH can positively modulate the consolidation of addiction-related learning, and that there are differences in the degree of post-reactivation lability exhibited by different forms of appetitive Pavlovian conditioning. These findings also demonstrate a surprising dissociation between the role of the NAcc in appetitive and aversive Pavlovian conditioning.

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