Ethanol-induced alterations in beta-endorphin levels in specific rat brain regions: modulation by adenosine agonist and antagonist.

Abstract

Previous studies in our laboratory have indicated that ethanol alters beta-endorphin (beta-EN) levels in specific rat brain regions. The present investigation was conducted to evaluate the effects of an adenosine agonist and an adenosine antagonist on these alterations. Male Sprague-Dawley rats weighing 150-200 g were used in this study. The animals were injected intraperitoneally at 11.00 h with ethanol (3 g/kg as a 22.5% w/v solution in saline), N6-cyclohexyladenosine (CHA; 0.1 mg/kg), theophylline (30 mg/kg), a combination of ethanol and CHA, or a combination of ethanol and theophylline. The control rats received saline. The animals were sacrificed 1 h after injection. Frontal cortex (CTX), hypothalamus (HY), hippocampus (HI), and midbrain (MB) were dissected, and their beta-EN levels were determined by radioimmunoassay. Ethanol administration significantly increased the beta-EN levels in HY (39% increase), HI (28% increase), and MB (19% increase), but had no effect in CTX. The adenosine agonist (CHA) produced similar significant increases in beta-EN levels in HY and MB, but did not alter these levels in CTX or HI. In contrast, the adenosine antagonist theophylline did not alter beta-EN levels in any brain region studied. However, theophylline pretreatment significantly reduced ethanol-induced changes in beta-EN levels in HY, completely blocked ethanol effects in HI, and reversed ethanol alterations in MB. On the other hand, CHA, concurrently administered with ethanol, potentiated ethanol-induced increases of beta-EN levels in HY and HI. These findings suggest that the ethanol-induced increases in beta-EN levels in specific rat brain regions may be modulated by adenosinergic compounds and that adenosine receptors may play a role in ethanol effects on rat brain levels of beta-EN.