Impaired alcohol-induced dopamine release in the nucleus accumbens in an inflammatory pain model: behavioral implications in male rats

Recent studies have drawn the attention to the link between alcohol use disorder and the presence of pain. Indeed, the correct management of pain in patients with a previous history of alcohol use disorder has been reported to decrease the risk of relapse in alcohol drinking, suggesting that in this prone population, pain may increase the vulnerability to relapse. Previous data in male rats revealed that inflammatory pain desensitizes mu-opioid receptors in the ventral tegmental area and increases intake of high doses of heroin. Owing to the relevant role of mu-opioid receptors in alcohol effects, we hypothesize that pain may also alter alcohol reinforcing properties and therefore affect alcohol relapse in male rats. Our microdialysis studies show that the presence of inflammatory pain blunted the increase of extracellular dopamine levels in the nucleus accumbens induced by 1.5 g/kg of ethanol (s.c.). Moreover, we also revealed that the administration of 52 nmol of ethanol into the ventral tegmental area failed to induce place preference only in inflammatory pain-suffering animals, and a higher dose (70 nmol) was necessary to reverse this effect. Finally, we evaluated the effect of inflammatory pain on the alcohol deprivation effect in long-term ethanol-experienced male rats. After 4 cycles of free ethanol intake and abstinence periods, inflammatory pain induced alcohol deprivation effect without affecting its magnitude. These intriguing data reveal the impact of pain on neurochemical and behavioral effects after alcohol administration but also underscore the necessity of finding an appropriate paradigm to determine the long-term behavioral consequences.