Effects of the trace amine associated receptor 1 agonist RO5263397 on abuse-related behavioral indices of methamphetamine in rats

Abstract

Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 (TAAR 1) is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of TAAR 1 agonists on addiction-related behavioral effects of methamphetamine is unknown. Methods: This study examined the effects of a TAAR 1 agonist RO5263397 on methamphetamine-induced behavioral sensitization, methamphetamine self-administration, cue- and methamphetamine-induced reinstatement of drug-seeking and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the TAAR 1 agonist RO5263397 (3.2-10 mg/kg). Results: RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue- and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. However, RO5263397 did not alter cue-induced reinstatement of sucrose-seeking behavior. Conclusions: Taken together, TAAR 1 agonists attenuate some abuse-related behavioral effects of methamphetamine, strongly suggesting that drugs activating TAAR 1 may be potentially useful for the treatment of methamphetamine addiction and warrant further studies