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

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), N-6-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 Ih 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 Hy, 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.