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

Janice Froehlich, Stephen M. Fischer, Emily R. Nicholson, Julian E. Dilley, Nicholas J. Filosa, Teal N. Smith, Logan C. Rademacher

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAlcoholism: Clinical and Experimental Research
DOIs
StateAccepted/In press - 2017

Fingerprint

Naltrexone
Genetic Predisposition to Disease
Alcohol Drinking
Alcohols
Drug therapy
Pharmaceutical Preparations
Rats
Varenicline
Alcoholism

Keywords

  • Alcohol Drinking
  • Naltrexone
  • P rats
  • Varenicline

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. / Froehlich, Janice; Fischer, Stephen M.; Nicholson, Emily R.; Dilley, Julian E.; Filosa, Nicholas J.; Smith, Teal N.; Rademacher, Logan C.

In: Alcoholism: Clinical and Experimental Research, 2017.

Research output: Contribution to journalArticle

Froehlich, Janice ; Fischer, Stephen M. ; Nicholson, Emily R. ; Dilley, Julian E. ; Filosa, Nicholas J. ; Smith, Teal N. ; Rademacher, Logan C. / A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking. In: Alcoholism: Clinical and Experimental Research. 2017.
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abstract = "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-na{\"i}ve 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-na{\"i}ve 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.",
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T1 - A Combination of Naltrexone + Varenicline Retards the Expression of a Genetic Predisposition Toward High Alcohol Drinking

AU - Froehlich, Janice

AU - Fischer, Stephen M.

AU - Nicholson, Emily R.

AU - Dilley, Julian E.

AU - Filosa, Nicholas J.

AU - Smith, Teal N.

AU - Rademacher, Logan C.

PY - 2017

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N2 - 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.

AB - 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.

KW - Alcohol Drinking

KW - Naltrexone

KW - P rats

KW - Varenicline

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