In:
Alcoholism: Clinical and Experimental Research, Wiley, Vol. 37, No. 8 ( 2013-08), p. 1278-1285
Abstract:
Animals that have chronically consumed alcohol and are subsequently deprived of it markedly increase their intake above basal levels when access to alcohol is reinstated. Such an effect, termed the alcohol deprivation effect ( ADE ), has been proposed to reflect (i) an obsessive–compulsive behavior, (ii) craving, or (iii) an increased reinforcing value of ethanol ( E t OH ). It has been reported that acetaldehyde, a highly reinforcing metabolite of E t OH , is generated in the brain by the action of catalase. Recent studies show that the administration of an anticatalase (sh RNA )‐encoding lentiviral vector into the brain ventral tegmental area ( VTA ) of naïve rats virtually abolishes (85 to 95%) their E t OH intake. It is hypothesized that the antireinforcing effect of the anticatalase vector will also inhibit the ADE . Methods Two‐month‐old W istar‐derived UC h B alcohol drinker rats were offered free access to water and 10 and 20% E t OH for 67 days. Thereafter, the animals were deprived of E t OH for 15 days and were subsequently offered access to the E t OH solutions. At the start of the deprivation period, animals were microinjected a single dose of an anticatalase (or control) vector into the VTA . E t OH intake was measured on the first hour of E t OH re‐exposure as well as on a 24‐hour basis for 7 days. Results A marked ADE was observed when E t OH intake was measured on the first hour or 24 hours following E t OH re‐exposure, compared to the corresponding controls. The administration of the anticatalase vector reduced ADE by 60 to 80% ( p 〈 0.001) on the first hour and by 63 to 80% ( p 〈 0.001) on the initial 24 hours of E t OH re‐exposure (first and second ADE , respectively) without changing the total fluid intake, indicating a specific effect on E t OH drinking. Conclusions Ethanol intake associated with ADE —a binge‐like drinking behavior—is markedly inhibited by the administration of an anticatalase vector into the VTA , which blocks the conversion of E t OH into acetaldehyde, strongly suggesting that the marked increased E t OH intake that follows an alcohol deprivation period is mediated by acetaldehyde and its reinforcing metabolite.
Type of Medium:
Online Resource
ISSN:
0145-6008
,
1530-0277
DOI:
10.1111/acer.2013.37.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2046886-6
detail.hit.zdb_id:
3167872-5
SSG:
15,3
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