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.