Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task

Abstract

Repeated amphetamine (AMPH) exposure is known to cause long-term changes in AMPH-induced locomotor behavior (i.e., sensitization) that are associated with similarly long-lasting changes in brain function. It is not clear, however, if such exposure produces long-lasting changes in a cognitive behavior that, in humans, is hypothesized to contribute to addiction. To examine whether repeated AMPH exposure induces both locomotor sensitization and alters impulsive choice in a delay-discounting task. Adult, male Sprague-Dawley rats (n = 29) were pretreated with 3.0 mg/kg AMPH or saline every other day for 20 days and were then trained to lever press for small, immediately delivered food reinforcement or larger reinforcements delivered after delays. We subsequently assessed the effects of acute AMPH (0.1-2.0 mg/kg) on delay-discounting. Lastly, we tested for long-lasting effects of pretreatment by giving an AMPH challenge (3.0 mg/kg) 1 week after the final delay-discounting session. Repeated AMPH produced sensitization to the drug's stereotypy-inducing effects but did not alter acquisition or baseline behavior in the delay-discounting task. Following acute AMPH, impulsive choice and other measures of delay-discounting were altered, but to a similar extent in both saline- and AMPH-pretreated groups. The AMPH challenge, given approximately 3 months after the last pretreatment injection, revealed that sensitization was still evident. Our results suggest that one behavioral consequence of repeated AMPH exposure-sensitization-does not overlap with another potential outcome-increased impulsivity. Furthermore, the neuroadaptations known to be associated with sensitization may be somewhat distinct from those that lead to changes in impulsive choice.