Methamphetamine-induced impulsivity during chronic methamphetamine treatment in rats: Effects of the TAAR 1 agonist RO5263397

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Impulsivity is an important personality trait associated with several clinical syndromes including drug abuse. While repeated drug exposure is known to increase certain behavioral responses, such as locomotion, to subsequent drug exposure, few studies have examined whether such sensitization develops for impulsive behavior. In the current study we tested the effects of methamphetamine acutely, during the course of, and upon discontinuation of chronic methamphetamine treatment on impulsive behavior in two models, the 5-choice serial reaction time task (5-CSRTT) and the delay-discounting task which measure impulsive action and impulsive choice, respectively. We also examined whether the trace amine-associated receptor 1 (TAAR1) agonist RO5263397 attenuated methamphetamine-induced effects in parallel tests. Acute methamphetamine dose-dependently increased premature responses in the 5-CSRTT and shifted the delay function upward in delay discounting. Up to 40 days of methamphetamine treatment did not significantly alter the dose-effect curve of methamphetamine-induced premature responses, but produced a significant effect in the delay-discounting task. RO5263397 attenuated acute methamphetamine-induced premature responses, but this effect became non-significant over the course of chronic treatment. RO5263397 did not significantly alter the delay-discounting performance. Discontinuation of methamphetamine treatment increased premature responses, which was attenuated by RO5263397, but did not significantly alter the delay discounting function. These results suggest that acute discontinuation from prolonged methamphetamine treatment increases impulsivity, which can be reduced by a TAAR1 agonist.HIGHLIGHTSRO5363397 attenuated premature responding induced by acute methamphetamine.Chronic methamphetamine produced robust locomotor sensitization.Impulsive behavior did not sensitize to chronic methamphetamine treatment.Discontinuation of chronic methamphetamine increased premature responding.The effect of methamphetamine discontinuation was attenuated by RO5263397.

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