Inhibition of naltrexone on relapse in methamphetamine self-administration and conditioned place preference in rats

Abstract

Methamphetamine (METH) addiction has been widely spread and caused severe problems both in society and public health in recent years, but there is a shortage of medication available. The naltrexone (NTX) as a non-selective opioid receptor antagonist has been widely applied to treat alcohol addiction and the relapse to opioid addiction after detoxification. In the present study, we investigated the potent pharmacotherapeutic effect of NTX in attenuating relapse to drug-seeking behavior in the METH self-administration and conditioned place preference (CPP) in rats. The results showed that acute intragastrical administration of NTX (40 mg/kg) significantly reduced cue-induced drug-seeking behavior after extinction training. The similar inhibition effect was observed in the CPP model, that the intragastrical administration of NTX (30 mg/kg) significantly disrupted the reactivation induced by intraperitoneal injection of METH (0.5 mg/kg) after the extinction training process. However, respective intragastrical administration of NTX (20 or 40 mg/kg) failed to alter the dose-response curve of METH under fixed ratio 2 program and intraperitoneal injection of METH (1.0 mg/kg)-induced reinstatement in rats self-administration. Overall, our findings suggest that NTX has the pharmacotherapeutic potential in reducing the relapse of METH addiction, which deserves further investigation as a promising medication for the treatment of METH addiction.

Keywords: Conditioned place preference; Methamphetamine; Naltrexone; Relapse; Self-administration.