Lession on the hypothalamic arcuate nucleus by estradiol valerate results in a blockade of ethanol-induced locomotion.

It has been suggested that the endogenous opioid system, especially b-endorphins (b-ep), can play a key role in the behavioral effects of ethanol. A single injection of estradiol valerate (EV) produces a neurotoxic effect on the b-endorphin cell population of the hypothalamic arcuate nucleus. In the present study we questioned whether mice pretreated with EV, exhibit any alterations in ethanol-induced behavioral effects. Female Swiss mice were pretreated with EV (2 mg/0.2 ml per mice) or vehicle and, 8 weeks later, these animals were challenged with ethanol (0.0-3.2 g/kg). Immediately after ethanol injection, mice were placed in the open field chambers and locomotor activity was assessed. EV administration did not produce any change in spontaneous locomotor activity but, conversely, blocked the locomotor activity induced by low (0.8 g/kg) and moderate (1.6 or 2.4 g/kg) doses of ethanol. Interestingly, the behavioral effects of higher doses of ethanol on locomotor activity as well as on the duration of the loss of righting reflex were unaffected by EV. Moreover, neither rota-rod performance or blood ethanol levels were affected by EV. In a second study, the effects of EV pre-treatment on caffeine- and 1-propanol-induced locomotor activity was tested. No differences were observed between groups in caffeine- or 1-propanol-induced locomotion. The results of the present study indicate that EV blocks ethanol-induced locomotor activity and that this effect can not be related with any difference in ethanol levels or nonspecific motor impairment. Furthermore, they suggest that b-ep containing neurons of the hypothalamic arcuate nucleus may play a role in some, but not all, behavioral effects of ethanol.