The influence of drugs of abuse on reward-based decision-making

Abstract

Animals are thought to learn from reinforcement by a dopamine-dependent reward prediction error, based on the difference between the expected and actual value of a reward. Here we demonstrate that this learning signal can be manipulated by drugs of abuse (amphetamine and Δ-9-tetrahydrocannabinol), resulting in reduced loss sensitivity on a competitive binary choice task. This effect is distinct from global choice strategy, as the randomness of choice responding is unaffected by drug and animals with on-board Δ-9-tetrahydrocannabinol are still capable of flexibly tracking changing reward contingencies. Furthermore, we demonstrate that lose-shift responding is increased following amphetamine sensitization. We propose this increase is indicative of drug-induced plastic changes facilitating a shift in behavioral control towards dorsolateral striatum. These results highlight the potential for drugs of abuse to alter reward-based decision-making and provide a novel measure of the shift in behavioral control towards dorsolateral striatum that is proposed to occur in addiction.