Centrally-formed acetaldehyde has been related to ethanol?s positive reinforcing effects. Lead (Pb), is a neurotoxicant that promotes drug addiction in rats. We have reported elevated ethanol consumption in a free-choice paradigm and increased ethanol self-administration in developmentally low-level Pb exposed rats. We propose that brain catalase-mediated ethanol metabolism to acetaldehyde would play a crucial role in these responses. In effect, aminotriazole (a catalase inhibitor) pretreatment blunted the increased ethanol intake, as well as the elevated catalase activity in the developmentally Pb-exposed rats that have consumed ethanol. Conversely, nitropropionic acid (a CAT activator) further increased voluntary ethanol intake in these animals as compared with controls, concomitantly with a slight elevation in catalase activity in absence of striatal neurotoxicity. Moreover, cyanamide (an ALDH antagonist), when administered systemically reversed the increased ethanol intake, while centrally-administered cyanamide had no effect. It is noteworthy that the hyperlocomotion manifested selectively in the Pb-exposed rats as a consequence of the ethanol consumed in the free-choice test is reversed by systemically administered cyanamide. These results suggest a participation of catalase, and consequently acetaldehyde, in Pb-induced high ethanol intake, and open up new avenues to elucidate the mechanism that underlies the Pb and ethanol interaction.
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