Performance on an impulse control task is altered in adult rats exposed to amphetamine during adolescence

Abstract

Repeated exposure to psychostimulant drugs is associated with long-lasting changes in cognition, particularly in behavioral tasks that are sensitive to prefrontal cortex function. Adolescents may be especially vulnerable to these drug-induced cognitive changes because of the widespread adaptations in brain anatomy and function that are characteristic of normal development during this period. Here, we used a differential reinforcement of low rates of responding task in rats to determine if amphetamine (AMPH) exposure during adolescence would alter behavioral inhibition in adulthood. Between postnatal days (PND) 27 and 45, rats received every other day injections of saline or AMPH (3 mg/kg). At PND 125, rats were trained progressively through a series of four reinforcement schedules (DRL 5, 10, 15, and 30 s) that required them to withhold responding for the appropriate amount of time before a lever press was reinforced. Relative to controls, AMPH-treated rats displayed transient deficits in behavioral inhibition (i.e., decreases in efficiency ratio) that were only evident at DRL 5. In addition, they had increased responding during nonreinforced periods, which suggested increased perseveration and propensity to attribute incentive salience to reward-paired cues. Following challenge injections with AMPH (.25-1 mg/kg, i.p.), which were given 10 min before the start of DRL 30 test sessions, both groups exhibited dose-dependent decreases in efficiency. These results suggest that AMPH-induced alterations in incentive-motivation and perseveration are more robust and longer-lasting than its effects on impulse control.