The effect of novelty on amphetamine self-administration in rats classified as high and low responders

Rationale: Rats categorized as high responders (HR) based on their activity in an inescapable novel environment self-administer more amphetamine than low responder (LR) rats. Previous research has also demonstrated that novel stimuli presented during the amphetamine self-administration session decreases the number of infusions earned. Objectives: This study determined whether individual differences in response to inescapable or free-choice novelty differentially predict the ability of novel stimuli to decrease amphetamine self-administration. Further, this study determined whether novel stimuli maintained the ability to reduce self-administration with repeated presentations, and whether the effect of novel stimuli varied as a function of the unit dose of amphetamine tested. Methods: Male rats were screened for their response in inescapable and free-choice novelty tests. Following initial training using a high unit dose of amphetamine (0.1 mg/kg per infusion), the dose was reduced (0.03 mg/kg per infusion), and novel stimuli were presented in the operant conditioning chamber on four separate sessions. In experiment 2, novel stimuli were presented during several sessions at a variety of amphetamine doses (0.003, 0.01, 0.03, and 0.056 mg/kg per infusion). Results: Four repeated presentations of novel stimuli reduced amphetamine self-administration with no significant loss in the effect of novel stimuli across repeated presentations. In experiment 2, novel stimuli reduced amphetamine self-administration at low unit doses (0.003 mg/kg and 0.01 mg/kg per infusion), and rats classified as HR based on their activity in inescapable novel stimuli were more disrupted by novel stimuli than LR rats. Conclusions: These results suggest that repeated presentation of novel stimuli can reduce amphetamine self-administration at low unit doses and that HR rats are more sensitive than LR rats to non-drug stimuli that compete with responding for amphetamine.