The effect of naltrexone on amphetamine-induced conditioned place preference and locomotor behaviour in the rat

Whereas amphetamine and other psychostimulants primarily act on the dopamine system, there is also evidence that other neurotransmitter systems, such as the endogenous opioid system, modulate psychostimulant-induced effects. Several studies have investigated the role of opioid antagonists on cocaine-induced conditioned place preference (CPP), but there is limited information about the interaction with amphetamines. The aim of the present study was to investigate the effect of the opioid receptor antagonist, naltrexone (NTX) on the conditioning, expression and reinstatement of amphetamine-induced place preference. In addition, the effect of NTX on locomotor behaviour was measured during all sessions. During training, animals were conditioned with amphetamine (2 mg/kg) to induce place preference. In order to extinguish the conditioned behaviour, animals received saline for 12 days. Reinstatement of CPP was induced by a priming dose of amphetamine (0.5 mg/kg). The interaction of NTX and amphetamine was evaluated using three paradigms of CPP: with NTX (vehicle, 0.3, 1.0 and 3.0 mg/kg) administered either 30 minutes prior to amphetamine conditioning, or 30 minutes before the expression, or 30 minutes before the amphetamine priming to induce reinstatement. Naltrexone had no effect on the conditioning, the expression or the reinstatement induced by a priming dose of amphetamine. Further, NTX by itself did not induce place preference or place aversion. In contrast, NTX significantly attenuated the locomotor response to a priming dose of amphetamine without affecting general locomotor behaviour. The results suggest differences in opioid modulation of amphetamine-induced behaviours in the rat.