Systemic administration of N-acetylcysteine during the extinction period and on the reinstatement day decreased the maintenance of morphine rewarding properties in the rats

Abstract

Many animal studies and early clinical trials suggested that N-acetylcysteine (NAC) may benefit addiction treatment. The present study tried to evaluate whether chronic administration of systemic NAC during the extinction period and acute administration of systemic NAC on the reinstatement day could reduce the maintenance of the morphine rewarding properties in the conditioned place preference (CPP) paradigm in the rats. Ninety-six adult male Wistar rats (190−220 g) were examined with morphine (7 mg/kg; sc) and saline (1 mL/kg; sc) during the 3-day conditioning phase in the CPP paradigm. After the acquisition of morphine CPP, different doses of NAC were daily administered during the extinction period (5, 10, 25, and 50 mg/kg; ip), or 30 min before the CPP test on the reinstatement day (2, 5, 10, 25, and 50 mg/kg; ip). Conditioning score and locomotor activity were recorded by the video tracking system and Ethovision software after acquisition on the post-conditioning day, the extinction period, and reinstatement day. Daily NAC administration in high doses (25 and 50 mg/kg; ip) reduced extinction-responding compared with the vehicle-control group during the extinction period. Although a single injection of NAC in doses 10, 25, 50 mg/kg decreased the reinstatement of morphine-induced CPP, two lower doses (2 and 5 mg/kg) could not significantly reduce the CPP scores. These are the first data suggesting that NAC's application during the extinction period could attenuate the morphine reward-associated behaviors in the rats. Moreover, NAC could inhibit the reinstatement of morphine CPP, which adds to the growing appreciation that the NAC may have potential therapeutic use in combating morphine dependence. It can be consistent with the hypothesis of the involvement of the glutamatergic system in the pathophysiology of addiction.