Naltrexone attenuates amphetamine-induced locomotor sensitization in the rat

ABSTRACT Amphetamine, and other stimulants, readily induces behavioral sensitization, an effect hypothesized to reflect neurobiological changes that may underlie certain aspects of drug addiction. Apart from the effects on the dopamine system, previous studies have also shown that amphetamine interacts with other neurotransmitters, including the endogenous opioid system. The unselective opioid receptor antagonist naltrexone (NTX) modulates amphetamine‐induced effects in both laboratory animals and humans. To further examine this interaction, the aim of the present study was to investigate the effect of NTX on the expression of locomotor sensitization and conditioned locomotor response in animals previously conditioned with amphetamine. Sensitization was induced by repeated administration of amphetamine (2 mg/kg) for 10 consecutive days. After a 10‐day drug‐free period, the rats were administered NTX (3 mg/kg) 30 minutes prior to the administration of a challenge dose of either amphetamine (0.5 mg/kg) (test for drug‐induced sensitization) or saline (test for conditioned locomotor response). NTX had no effect on acute amphetamine‐induced locomotor activity or on general locomotor activity in animals without a history of amphetamine conditioning. However, animals previously conditioned with amphetamine showed a sensitized locomotor response to the amphetamine challenge following the 10‐day drug‐free period. This sensitized response was significantly inhibited by NTX pre‐treatment. In addition, NTX pre‐treatment blocked the conditioned locomotor response when the amphetamine‐conditioned animals were placed in the previously amphetamine‐paired context. This study showed that NTX attenuates drug‐ and cue‐induced locomotor behavior in amphetamine‐conditioned animals, supporting recent clinical findings that indicated a potential role of NTX as a treatment for amphetamine dependence.