The opioid receptor antagonist naltrexone attenuates reinstatement of amphetamine drug-seeking in the rat

Amphetamine produces its rewarding effects by enhancing dopamine transmission in the mesocorticolimbic pathway. Several studies have also suggested the involvement of the endogenous opioid system in mediating the neurochemical and behavioural effects of amphetamine. The aim of this study was to investigate the effect of the unselective opioid receptor antagonist naltrexone (NTX) on reinstatement of amphetamine self-administration in the rat. Animals were trained to self-administer amphetamine under a fixed ratio 1 (FR1) schedule (0.1 mg/kg/infusion). After receiving a stable drug intake the amphetamine was replaced with saline and the animals went through an extinction period. After reaching the extinction criteria, animals were pre-treated with NTX (0, 0.3, 1.0 and 3.0 mg/kg, S.C.) 30 min before giving a priming dose of amphetamine (0.5 mg/kg s.c). To study the effects of NTX on operant behaviour, animals were trained to lever press for food pellets under a FR1 schedule of reinforcement. Results from the present study shows that a single injection of amphetamine reinstated self-administration behaviour. NTX (0.3 and 1.0 mg/kg) significantly attenuated the amphetamine-induced reinstatement but NTX had no effect at any dose studied on food taking behaviour. These results show that NTX attenuates reinstatement of amphetamine self-administration in rats without suppressing general behaviour, implicating a functional role for opioid receptors in modulating amphetamine seeking behaviour. (c) 2008 Elsevier B.V. All rights reserved.