Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.
BACKGROUND
Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission.


METHODS
Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values.


RESULTS
The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol.


CONCLUSIONS
This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are discussed together with previous findings suggesting a putative linkage between brain ethanol metabolism and the endogenous opioid system to explain some of the neuroendocrine effects of ethanol.
Pastor
Raúl
R
Area de Psicobiología, Universitat Jaume I, Campus de Riu Sec, 12071 Castelló, Spain.
Sanchis-Segura
Carles
C
Aragon
Carlos M G
CM
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000431:Ethanol; D009271:Naltrexone; D002374:Catalase; D003345:Corticosterone