Effect of acetaldehyde on acute tolerance and ethanol consumption in drinker and nondrinker rats.
OBJECTIVE
Acetaldehyde (AcH) has been shown to have aversive or reinforcing actions in relation to ethanol consumption. We have previously observed that a pharmacological dose of AcH (50-150 mg/kg) administered intraperitoneally (i.p.) produced a dose-dependent flavor aversion in low-ethanol drinker (UChA) rats, whereas high-ethanol drinker (UChB) rats appeared to be insensitive to AcH. Both strains of rats differ innately in their brain aldehyde dehydrogenase (ALDH) activity and in their capacity to develop acute tolerance to ethanol. The present study evaluates the effects of AcH, in UChA and UChB rats, on rats' behavior, their voluntary ethanol consumption and the development of acute functional tolerance to motor impairment induced by a dose of ethanol.


METHODS
Subjects were rats selectively bred for high (UChB; n = 48) and low (UChA; n = 40) voluntary ethanol consumption. Rats were treated with either saline or doses of AcH (50 or 100 mg/kg, i.p.), and examined for effects on motor activity, on voluntary alcohol consumption with free access to a 10% alcohol solution and on acute tolerance to motor impairment induced by an ethanol dose (2.3 g/kg, i.p.), using the tilting plane test.


RESULTS
AcH, 50 or 100 mg/kg, caused a dose-dependent loss of the righting reflex in UChA rats, whereas in UChB rats with same dose, a slight excitement was observed. There was significant increase of voluntary ethanol consumption in UChB rats (p < .001) 17 hours after the AcH injection, compared with saline-treated and control rats; in UChA rats, no change in voluntary ethanol consumption was produced. AcH produced a faster acute tolerance-to-ethanol development in UChB rats (p < .001) as compared with saline-treated and control rats, and no change in acute tolerance in UChA rats. Acetaldehyde injection did not change total mitochondrial ALDH2 activity.


CONCLUSIONS
These results show that, 17 hours later, treatment of rats with pharmacological doses of acetaldehyde alters the voluntary ethanol consumption and acute tolerance development in UChB but not UChA rats. One of the factors involved may be a different sensitivity to AcH in these rat strains.
Tampier
Lutske
L
Institute of Biomedical Sciences, School of Medicine, University of Chile, Santiago. ltampier@machi.med.uchile.cl
Quintanilla
María Elena
ME
D000079:Acetaldehyde / Q000097:blood / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000503:physiopathology*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity
D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde