Opposite effects of acute versus chronic naltrexone administration on ethanol-induced locomotion

Several studies have pointed out that the mu opioid receptor (MOR) can play a key role in some of the behavioural effects of ethanol. In the present study, the implication of the MOR in ethanol-induced locomotion in mice was assessed. First, the effects of the administration of different naltrexone doses (0.001-1.000 mg/kg) on the locomotor changes produced by ethanol (2.5 g/kg) were evaluated. In a second set of experiments, the ability of repeated naltrexone (6 mg/kg) administrations to modify the effects of ethanol was also assessed on mice locomotion. The results of the present study revealed that an acute naltrexone administration reduced dose-dependently ethanol-induced locomotion. Conversely, after repeated naltrexone injections, a transient boost of ethanol induced locomotor activity was observed. Thus, the results of the present study revealed that the effects of these naltrexone pretreatments on ethanol-induced locomotion are similar to the previously described changes on MOR activity. Moreover, the same (acute and chronic) naltrexone pretreatments produced similar changes on the locomotion of mice after a challenge with morphine (a MOR agonist), but not after tert-butanol (an alcohol which does not release beta-endorphins) administration. Therefore, our results are discussed in terms of the proved ability of ethanol to promote the release of beta-endorphins and, consequently, to activate the MOR.