Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion.
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.
Spivak
K
K
Center for Studies on Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Aragon
C M
CM
Amit
Z
Z
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D003213:Conditioning, Psychological; D003484:Cyanamide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D000077604:Fomepizole; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D012439:Saccharin; D013649:Taste / Q000187:drug effects*
D011720:Pyrazoles; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; D012439:Saccharin; D000079:Acetaldehyde