A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. - OpacWWW

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Tytuł:: A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking.
Autorzy:: Froehlich JC; Indiana University School of Medicine , Indianapolis, Indiana.
Fischer SM; Mayo Clinic , Rochester, Minnesota.
Nicholson ER; Indiana University School of Medicine , Indianapolis, Indiana.
Dilley JE; Indiana University School of Medicine , Indianapolis, Indiana.
Filosa NJ; Indiana University School of Medicine , Indianapolis, Indiana.
Smith TN; Indiana University School of Medicine , Indianapolis, Indiana.
Rademacher LC; Indiana University School of Medicine , Indianapolis, Indiana.
Źródło:: Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2017 Mar; Vol. 41 (3), pp. 644-652. Date of Electronic Publication: 2017 Feb 09.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Publication: Oxford, UK : Wiley-Blackwell
Original Publication: New York, N.Y. : Grune & Stratton, c1977-
MeSH Terms:: Alcohol Drinking/*drug therapy
Alcohol Drinking/*genetics
Genetic Predisposition to Disease/*genetics
Naltrexone/*administration & dosage
Varenicline/*administration & dosage
Animals ; Drug Therapy, Combination ; Male ; Narcotic Antagonists/administration & dosage ; Nicotinic Agonists/administration & dosage ; Rats
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Grant Information:: P50 AA007611 United States AA NIAAA NIH HHS; P60 AA007611 United States AA NIAAA NIH HHS; R01 AA021208 United States AA NIAAA NIH HHS
Contributed Indexing:: Keywords: Alcohol Drinking; Naltrexone; P rats; Varenicline
Substance Nomenclature:: 0 (Narcotic Antagonists)
0 (Nicotinic Agonists)
5S6W795CQM (Naltrexone)
W6HS99O8ZO (Varenicline)
Entry Date(s):: Date Created: 20170106 Date Completed: 20171219 Latest Revision: 20240324
Update Code:: 20240324
PubMed Central ID:: PMC5332282
DOI:: 10.1111/acer.13326
PMID:: 28055135
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Background: This study examined whether naltrexone (NTX) or varenicline (VAR), alone or in combination, can retard the phenotypic expression of a genetic predisposition toward high alcohol drinking in rats selectively bred for high alcohol intake when drug treatment is initiated prior to, or concomitantly with, the onset of alcohol drinking.
Methods: Alcohol-naïve P rats were treated daily with NTX (15.0 mg/kg BW), VAR (1.0 mg/kg BW), a combination of NTX (15.0 mg/kg BW) + VAR (1.0 mg/kg BW), or vehicle (VEH) for 2 weeks prior to, or concomitantly with, their first opportunity to drink alcohol and throughout 21 days of daily 2-hour alcohol access. Drug treatment was then discontinued for 3 weeks followed by reinstatement of drug treatment for an additional 3 weeks.
Results: When P rats were pretreated with drug for 2 weeks prior to onset of alcohol access, only NTX + VAR in combination blocked the acquisition of alcohol drinking in alcohol-naïve P rats. When drug treatment was initiated concomitantly with the first opportunity to drink alcohol, NTX alone, VAR alone, and NTX + VAR blocked the acquisition of alcohol drinking. Following termination of drug treatment, NTX + VAR and VAR alone continued to reduce alcohol drinking but by the end of 3 weeks without drug treatment, alcohol intake in all groups was comparable to that seen in the vehicle-treated group as the expression of a genetic predisposition toward high alcohol drinking emerged in the drug-free P rats. After 3 weeks without drug treatment, reinstatement of NTX + VAR treatment again reduced alcohol intake.
Conclusions: A combination of NTX + VAR, when administered prior to, or concomitantly with, the first opportunity to drink alcohol, blocks the acquisition of alcohol drinking during both initial access to alcohol and during a later period of alcohol access in P rats with a genetic predisposition toward high alcohol intake. The results suggest that NTX + VAR may be effective in curtailing alcohol drinking in individuals at high genetic risk of developing alcoholism.
(Copyright © 2017 by the Research Society on Alcoholism.)

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A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking.