Antinociceptive effects of alcohol and nicotine: involvement of the opioid system

Both alcohol and nicotine have been shown to possess antinociceptive or analgesic effects. An additive or synergistic antinociceptive effect induced by simultaneous administration of alcohol and nicotine could further contribute to their co-abuse. In this study, we sought to evaluate the antinociceptive effects of various combinations of ethanol and nicotine and to determine whether these effects could be blocked by an opioid antagonist. Adult male Wistar rats were treated with various doses of alcohol (0.1-2 g/kg), nicotine (0.01-2 mg/kg) or their combination and their behavior in tail flick test, reflective of spinal antinociception and hotplate test, mainly reflective of supraspinal antinociception were evaluated. Alcohol at the highest dose of 2 g/kg resulted in significant antinociceptive effects in both assays. Nicotine at 1 mg/kg resulted in significant antinociception in the hotplate; however, in the tail flick test a dose of 2 mg/kg was required for an antinociceptive effect. Combination of doses of alcohol and nicotine that were ineffective by themselves resulted in antinociceptive responses in both paradigms. These effects were attenuated by pretreatment with the non-selective opioid receptor antagonist naloxone. The data indicate that a combination of alcohol and nicotine can result in a synergistic antinociceptive response that is at least partially mediated by the opioid system. The analgesic effects induced by combination of alcohol and nicotine may be a contributory factor in their co-abuse.