The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

Repeated exposure to psychostimulants alters behavioral responses to reward-related cues; however, the motivational underpinnings of this effect have not been fully characterized. The following study was designed to examine how amphetamine sensitization affects performance in rats on a series of Pavlovian and operant tasks that distinguish between general-incentive and outcome-selective forms of conditioned responses. Adult male rats underwent Pavlovian and instrumental training for food pellet rewards. Following training, rats were sensitized to d-amphetamine (2 mg/kg for 7 days). Rats were subsequently tested on an outcome-selective Pavlovian-instrumental transfer (PIT) task, an outcome-reinstatement task, and an outcome devaluation task. Additionally, in a separate experiment, PIT was assessed in amphetamine-sensitized and control rats using a Pavlovian backward-conditioned stimulus. Repeated amphetamine exposure sensitized locomotor activity to acute amphetamine challenge. Amphetamine altered responses to CS presentations by increasing conditioned approach. During tests of PIT, amphetamine-treated rats showed no outcome-selectivity in their responding, responding to a CS whether or not it shared a common outcome with the instrumental response. No effect of amphetamine sensitization was observed on tests of outcome-selective reinstatement by outcome delivery or action selection based on outcome value. Amphetamine-sensitized rats showed impaired outcome-selective PIT to a backward CS but were unaltered in conditioned approach. Amphetamine sensitization prevents outcome-selective responding during PIT, which is dissociable from amphetamine's effects on conditioned approach. These data suggest fundamental alterations in how stimuli motivate action in addiction.