Development of an alcohol deprivation and escalation effect in C57BL/6J mice.

BACKGROUND Relapse-like drinking has been studied through the expression of the alcohol deprivation effect (ADE), which is measured by a pronounced increase in ethanol preference and consumption after imposed abstinence. No studies have characterized the ADE in C57BL/6J (B6) mice. The present study examined the effects of length and number of deprivations on the expression of the ADE in B6 mice. METHODS Adult male B6 mice received 24-hour continuous access to ethanol and water for 6 weeks (baseline). Experiment 1 determined the ADE in mice receiving weekly access to 15% ethanol (i.e., exposed 1 day a week and deprived during the other 6 days) for a total of 10 weeks. Experiments 2 and 3 determined the ADE after a single 2-week deprivation period in mice receiving a single concentration of 15% ethanol or multiple concentrations of 7.5, 15, and 30% ethanol, respectively, followed by weekly access to their respective ethanol solutions for 10 weeks. Experiment 4 determined the ADE after a single 2-week deprivation period, followed by daily access to 15% ethanol. Mice never deprived of ethanol (i.e., continuous access) were used as age-matched drinking controls. RESULTS The ADE was observed after the initial 6-day deprivation period and was profoundly enhanced (i.e., escalation of the ADE) following weekly reexposure to 15% ethanol. Compared with a single concentration of 15% ethanol, concurrent access to multiple ethanol concentrations resulted in a near 2-fold increase in baseline ethanol consumption. Regardless of having access to single or multiple concentrations of ethanol, the ADE was not observed immediately after a 2-week deprivation period. The ADE was observed (although to a lesser magnitude and duration) following weekly reexposure to single or multiple concentrations of ethanol. Alternatively, following a 2-week deprivation period, mice receiving daily access to 15% ethanol showed a significant decrease in ethanol intake and preference (i.e., negative ADE). CONCLUSIONS Short-term deprivations followed by repeated intermittent (weekly) reexposure to ethanol produces a robust ADE in B6 mice. Increasing the initial deprivation length to 2 weeks produces various opposing effects, including erasure of an initial ADE, diminished expression and magnitude of the ADE following weekly exposure, and complete reversal of the ADE following daily exposure to ethanol.

[1]  A. Zapata,et al.  Repeated Ethanol Intoxication Induces Behavioral Sensitization in the Absence of a Sensitized Accumbens Dopamine Response in C57BL/6J and DBA/2J Mice , 2006, Neuropsychopharmacology.

[2]  H. Becker,et al.  Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice. , 2004, Alcoholism, clinical and experimental research.

[3]  W. Mcbride,et al.  Recent advances in animal models of alcohol craving and relapse , 2004, Pharmacology Biochemistry and Behavior.

[4]  J. Crabbe,et al.  Pharmacogenetic studies of alcohol self-administration and withdrawal , 2004, Psychopharmacology.

[5]  Ting-kai Li,et al.  Effects of concurrent access to a single concentration or multiple concentrations of ethanol on ethanol intake by periadolescent high-alcohol-drinking rats. , 2004, Alcohol.

[6]  D. Morgan,et al.  Sensitization to the reinforcing effects of cocaine following binge-abstinent self-administration , 2004, Neuroscience & Biobehavioral Reviews.

[7]  P. Kalivas,et al.  Chronic ethanol consumption by C57BL/6 mice promotes tolerance to its interoceptive cues and increases extracellular dopamine, an effect blocked by naltrexone. , 2003, Alcoholism, clinical and experimental research.

[8]  C. O'brien.  Research advances in the understanding and treatment of addiction. , 2003, The American journal on addictions.

[9]  Ting-kai Li,et al.  Effects of Repeated Alcohol Deprivations on Operant Ethanol Self-Administration by Alcohol-Preferring (P) Rats , 2003, Neuropsychopharmacology.

[10]  Ting-kai Li,et al.  Phenotypic and Genotypic Characterization of the Indiana University Rat Lines Selectively Bred for High and Low Alcohol Preference , 2002, Behavior genetics.

[11]  G. Koob,et al.  Neurobiological evidence for hedonic allostasis associated with escalating cocaine use , 2002, Nature Neuroscience.

[12]  W. Mcbride,et al.  Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of alcohol-preferring rats. , 2001, Alcoholism, clinical and experimental research.

[13]  R. Spanagel,et al.  Long-term ethanol self-administration with repeated ethanol deprivation episodes changes ethanol drinking pattern and increases anxiety-related behaviour during ethanol deprivation in rats , 1998, Behavioural pharmacology.

[14]  D. Dibattista.  Examination of the negative alcohol-deprivation effect in the golden hamster (Mesocricetus auratus). , 1991, Alcohol.

[15]  J. Sinclair,et al.  A negative alcohol-deprivation effect in hamsters. , 1973, Quarterly journal of studies on alcohol.

[16]  Sinclair Jd,et al.  Development of an alcohol-deprivation effect in rats. , 1968 .

[17]  G. Mcclearn,et al.  Mouse strain differences in preference for various concentrations of alcohol. , 1962, Quarterly journal of studies on alcohol.

[18]  R. Spanagel.  Recent Animal Models of Alcoholism , 2000, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[19]  J. Sinclair,et al.  Lack of alcohol-deprivation effect in AA rats. , 1988, Alcohol.