Cognitive factors in addiction and nucleus accumbens function: Some hints from rodent models

Abstract

Elevation of extracellular dopamine levels in the nucleus accumbens is important for both the initiation and the maintenance of cocaine and heroin seeking in animal models. Nucleus accumbens neurons fire in response to both the receipt and the expectancy of reward. The learning of drug self- administration habits depends critically on the ability of the animal to learn associations between rewards and their environmental predictors, and such learning does not occur in accumbens-compromised animals. Reward- associated stimuli are also critical for the initiation of drug taking following periods of abstinence in trained animals. Reward-associated stimuli are also important in maintaining continued responding for these drugs, although once extracellular dopamine levels have become elevated by initial drug intake, subsequent drug self-administration becomes increasingly dominated by pharmacological factors, at least in rodent models. Initially rewarding drug injections appear to lose their rewarding effectiveness when dopamine concentration in the nucleus accumbens is elevated above some satiating level. When dopamine is depleted or dopamine function is impaired, the probability of response initiation decreases; rats do not appear to self- medicate depression of the reward system as humans have been suggested to do. This presumed difference between the two species may reflect cognitive functions unique to humans, such as insight gained from the observation of others and response biases conferred through language and culture. Thus, although they inform us regarding some cognitive factors in addiction and nucleus accumbens function, our animal models may inform us minimally about cognitive factors that are of major significance in humans.