Document Detail


GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.
MedLine Citation:
PMID:  21895721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed.
METHODS: Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period.
RESULTS: During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions.
CONCLUSIONS: These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history as an important variable in the liability for alcohol abuse.
Authors:
Mary W Hulin; Russell J Amato; Peter J Winsauer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-06
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  36     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-30     Completed Date:  2012-05-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  223-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 by the Research Society on Alcoholism.
Affiliation:
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Science Center, New Orleans, Louisiana, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology*
Alcohol Drinking / psychology*
Animals
Data Interpretation, Statistical
Dehydroepiandrosterone / pharmacology
Dose-Response Relationship, Drug
Eating / drug effects
Lorazepam / pharmacology
Male
Rats
Rats, Long-Evans
Receptors, GABA-A / drug effects*
Saccharin / pharmacology
Grant Support
ID/Acronym/Agency:
AA019848/AA/NIAAA NIH HHS; F30 AA019848-01/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, GABA-A; 53-43-0/Dehydroepiandrosterone; 81-07-2/Saccharin; 846-49-1/Lorazepam
Comments/Corrections

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