Methamphetamine-disrupted sensory processing mediates conditioned place preference performance

Abstract

Drug memory plays an important role in priming subsequent drug use. We used drug-induced conditioned place preference (CPP) as a paradigm to study such drug memory. In this paradigm, repeated association of specific environmental cues with abused drug-induced subjective euphoria has been suggested to motivate later biased approaching behavior toward the euphoria-linked environment at a drug-free status. Our previous report indicated that formation of methamphetamine-induced CPP was independent of de novo protein synthesis. We suspected that methamphetamine-produced effects independent of its hedonic value may be responsible for the drug-induced place preference. One such possibility was that methamphetamine treatment directly disrupted the sensory encoding process and rodents’ novelty-seeking propensity consequently determined the biased place performance. We observed that mice undergoing three times of methamphetamine and compartment pairings exhibited similar compartment preference as those with only one or two methamphetamine-compartment pairings even though they all experienced three vehicle-compartment pairings. Moreover, 30 min before the CPP test, single methamphetamine injection at a dose of 1 mg/kg abolished methamphetamine (1 mg/kg)-induced CPP, while one dose of cocaine (5 mg/kg) did not affect cocaine (5 mg/kg)-induced CPP under a similar protocol. Finally, pretreatment with 1 mg/kg of methamphetamine impaired the spontaneous alteration and recognition performance in Y maze task and impeded the object recognition performance. Taken together, we conclude that methamphetamine-induced CPP performance may be, in part, caused by methamphetamine-impaired sensory processing.