Effect of Mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking

S. Krishnan-Sarin; G. S. Wand; X. W. Li; P. S. Portoghese; J. C. Froehlich

doi:10.1016/S0091-3057(97)00474-7

Effect of Mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking

S. Krishnan-Sarin, G. S. Wand, X. W. Li, P. S. Portoghese, J. C. Froehlich

School of Medicine

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

Abstract

Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line) Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta- FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messinger ribonucleic acid - mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.

Original language	English (US)
Pages (from-to)	627-635
Number of pages	9
Journal	Pharmacology Biochemistry and Behavior
Volume	59
Issue number	3
DOIs	https://doi.org/10.1016/S0091-3057(97)00474-7
State	Published - Mar 1998

Keywords

Alcohol drinking
Alcohol preference
Beta-FNA
Genetic selection
Opioid antagonists
Opioid receptors
Pituitary gland
Rats
mRNA

ASJC Scopus subject areas

Biochemistry
Toxicology
Pharmacology
Clinical Biochemistry
Biological Psychiatry
Behavioral Neuroscience

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10.1016/S0091-3057(97)00474-7

Cite this

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title = "Effect of Mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking",

abstract = "Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line) Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta- FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messinger ribonucleic acid - mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.",

keywords = "Alcohol drinking, Alcohol preference, Beta-FNA, Genetic selection, Opioid antagonists, Opioid receptors, Pituitary gland, Rats, mRNA",

author = "S. Krishnan-Sarin and Wand, {G. S.} and Li, {X. W.} and Portoghese, {P. S.} and Froehlich, {J. C.}",

note = "Funding Information: This research was supported, in part, by grants AA08312, AA08553, AA07611, and DA01533 from the PHS. We thank Dr. James Norton for statistical consultation and Dr. Ting-Kai Li for supplying us with selectively bred rats from the P, NP, and HAD lines. ",

year = "1998",

month = mar,

doi = "10.1016/S0091-3057(97)00474-7",

language = "English (US)",

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AU - Krishnan-Sarin, S.

AU - Wand, G. S.

AU - Li, X. W.

AU - Portoghese, P. S.

AU - Froehlich, J. C.

N1 - Funding Information: This research was supported, in part, by grants AA08312, AA08553, AA07611, and DA01533 from the PHS. We thank Dr. James Norton for statistical consultation and Dr. Ting-Kai Li for supplying us with selectively bred rats from the P, NP, and HAD lines.

PY - 1998/3

Y1 - 1998/3

N2 - Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line) Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta- FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messinger ribonucleic acid - mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.

AB - Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but not water intake in a dose-dependent manner in rats selectively bred for high alcohol intake (HAD line) Beta-FNA also suppressed the intake of a saccharin solution containing alcohol without altering the intake of a similar solution without alcohol. The results suggest that beta- FNA may prove useful as a pharmacotherapeutic agent for the treatment of alcohol dependence. In a second study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC messinger ribonucleic acid - mRNA) was compared in another pair of rat lines selectively bred for high or low alcohol intake (alcohol-preferring or P and alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the anterior and neurointermediate lobes of the pituitary of P rats compared with NP rats. The results suggest that a genetic predisposition toward high alcohol drinking may be associated with increased responsiveness of the opioid system to alcohol.

KW - Alcohol drinking

KW - Alcohol preference

KW - Beta-FNA

KW - Genetic selection

KW - Opioid antagonists

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KW - Pituitary gland

KW - Rats

KW - mRNA

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Effect of Mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking

Abstract

Keywords

ASJC Scopus subject areas

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