Ethanol injected into the hypothalamic arcuate nucleus induces behavioral stimulation in rats: an effect prevented by catalase inhibition and naltrexone.
It is suggested that some of the behavioral effects of ethanol, including its psychomotor properties, are mediated by beta-endorphin and opioid receptors. Ethanol-induced increases in the release of hypothalamic beta-endorphin depend on the catalasemic conversion of ethanol to acetaldehyde. Here, we evaluated the locomotor activity in rats microinjected with ethanol directly into the hypothalamic arcuate nucleus (ArcN), the main site of beta-endorphin synthesis in the brain and a region with high levels of catalase expression. Intra-ArcN ethanol-induced changes in motor activity were also investigated in rats pretreated with the opioid receptor antagonist, naltrexone (0-2 mg/kg) or the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg). We found that ethanol microinjections of 64 or 128, but not 256 microg, produced locomotor stimulation. Intra-ArcN ethanol (128 microg)-induced activation was prevented by naltrexone and AT, whereas these compounds did not affect spontaneous activity. The present results support earlier evidence indicating that the ArcN and the beta-endorphinic neurons of this nucleus are necessary for ethanol to induce stimulation. In addition, our data suggest that brain structures that, as the ArcN, are rich in catalase may support the formation of ethanol-derived pharmacologically relevant concentrations of acetaldehyde and, thus be of particular importance for the behavioral effects of ethanol.
Pastor
Raúl
R
Area de Psicobiología, Universitat Jaume I, Castelló, Spain.
Aragon
Carlos M G
CM
D000079:Acetaldehyde / Q000493:pharmacokinetics; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000201:enzymology; D001143:Arousal / Q000187:drug effects*; D002374:Catalase / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D001615:beta-Endorphin / Q000378:metabolism*
D009292:Narcotic Antagonists; D000431:Ethanol; D009271:Naltrexone; D001615:beta-Endorphin; D002374:Catalase; D000079:Acetaldehyde; D000640:Amitrole