Systemic and intra-accumbens microinjections of naltrexone interfere with tolerance to ethanol in rats

Rationale Evidence suggests a role for the opioid system in the control of ethanol reinforcement and drinking. Previous findings have shown that naltrexone, an opioid antagonist that decreases ethanol consumption in humans and experimental animals, reduces the acquisition of acute ethanol tolerance in rats. However, there are few data regarding the role of the opioid system in the acquisition of ethanol tolerance, particularly in brain areas involved in the rewarding actions of ethanol. Objectives This study investigates the effects of systemic and of intra-accumbens injections of naltrexone on the development of rapid tolerance to ethanol. Methods Wistar rats received intraperitoneal injections of naltrexone (0.1–3.0 mg/kg) or microinjections into the core or shell portions of the nucleus accumbens (5–20 μg) before ethanol (2.7 g/kg i.p.). The animals were tested for motor coordination on the tilting plane apparatus. Tolerance was assessed 24 h later by administering the same dose of ethanol to all animals and retesting them on the tilting plane. Results The second injection of ethanol resulted in less motor incoordination on Day 2, suggesting the development of rapid tolerance. Pretreatment with naltrexone, either i.p. (0.3 and 0.6 mg/kg) or intra-accumbens (5–20 μg), on Day 1, blocked the development of rapid tolerance to the motor-incoordinating effects of ethanol on Day 2 without affecting the motor performance of the animals on Day 1. Conclusions The results suggest that the opioid system may be involved in the development of ethanol tolerance, and that the nucleus accumbens may play a role in this phenomenon.