The alcohol-preferring P rat and animal models of excessive alcohol drinking

被引:246
作者
Bell, Richard L.
Rodd, Zachary A.
Lumeng, Lawrence
Murphy, James M.
McBride, William J.
机构
[1] Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA
关键词
genetic; selection; ethanol; reward; reinforcement; conditioning;
D O I
10.1111/j.1369-1600.2005.00029.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking.
引用
收藏
页码:270 / 288
页数:19
相关论文
共 174 条
[21]  
Childress A R, 1993, NIDA Res Monogr, V137, P73
[22]  
CHOU SP, 1992, BRIT J ADDICT, V87, P1199
[23]   Long-lasting resistance to extinction of response reinstatement induced by ethanol-related stimuli: Role of genetic ethanol preference [J].
Ciccocioppo, R ;
Angeletti, S ;
Weiss, F .
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH, 2001, 25 (10) :1414-1419
[24]  
CICERO TJ, 1979, BIOCH PHARMACOLOGY E, V2, P533
[25]   NEUROGENETIC ADAPTIVE-MECHANISMS IN ALCOHOLISM [J].
CLONINGER, CR .
SCIENCE, 1987, 236 (4800) :410-416
[26]  
Cloninger CR., 1996, IMPULSIVITY COMPULSI, P59
[27]   DRD2 genotypes and substance use in adolescent children of alcoholics [J].
Conner, BT ;
Noble, EP ;
Berman, SM ;
Ozkaragoz, T ;
Ritchie, T ;
Antolin, T ;
Sheen, C .
DRUG AND ALCOHOL DEPENDENCE, 2005, 79 (03) :379-387
[28]  
Conrod PJ, 1997, ALCOHOL CLIN EXP RES, V21, P140
[29]   Differential sensitivity to alcohol reinforcement in groups of men at risk for distinct alcoholism subtypes [J].
Conrod, PJ ;
Pihl, RO ;
Vassileva, J .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1998, 22 (03) :585-597
[30]   AUTONOMIC REACTIVITY AND ALCOHOL-INDUCED DAMPENING IN MEN AT RISK FOR ALCOHOLISM AND MEN AT RISK FOR HYPERTENSION [J].
CONROD, PJ ;
PIHL, RO ;
DITTO, B .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 1995, 19 (02) :482-489