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Alterations in Brain Aldehyde Dehydrogenase Activity Modify Ethanol‐induced Conditioned Taste Aversion
Author(s) -
Spivak Karen,
Aragon Carlos M. G.,
Amit Zalman
Publication year - 1987
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1987.tb00163.x
Subject(s) - cyanamide , aldehyde dehydrogenase , acetaldehyde , chemistry , ethanol , intraperitoneal injection , saccharin , pharmacology , alcohol dehydrogenase , biochemistry , endocrinology , medicine , enzyme
The role of peripherally and centrally acting acetaldehyde in ethanol‐induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4‐methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water‐deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4‐methylpyrazole (4MP+S), cyanamide (S+C), or 4‐methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide‐treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide‐treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol‐induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.