Acute effects of Naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice
- First Online:
Recently, a simple procedure was described, drinking in the dark (DID), in which C57BL/6J mice self-administer ethanol to the point of intoxication. The test consists of replacing the water with 20% ethanol in the home cage for 2 or 4 h early during the dark phase of the light/dark cycle.
To determine whether the model displays predictive validity with naltrexone, and whether opioid or dopaminergic mechanisms mediate excessive drinking in the model.
Materials and methods
Naltrexone or GBR 12909 were administered via intraperitoneal injections immediately before offering ethanol solutions, plain tap water, or 10% sugar water to male C57BL/6J mice, and consumption was monitored over a 2- or 4-h period using the DID procedure.
Naltrexone (0.5, 1, or 2 mg/kg) dose dependently decreased ethanol drinking but these same doses had no significant effect on the consumption of plain water or 10% sugar water. GBR 12909 (5, 10, and 20 mg/kg) dose dependently reduced the consumption of ethanol and sugar water but had no effect on plain water drinking.
The DID model demonstrates predictive validity. Both opioid and dopamine signaling are involved in ethanol drinking to intoxication. Different physiological pathways mediate high ethanol drinking as compared to water or sugar water drinking in DID. DID may be a useful screening tool to find new alcoholism medications and to discover genetic and neurobiological mechanisms relevant to the human disorder.
KeywordsAlcoholism Naltrexone GBR 12909 Ethanol C57BL/6J Drinking Natural reward Water Opioid Dopamine
- Cicero T (1980) Alcohol self-administration, tolerance and withdrawal in humans and animals: theoretical and methodological issues. In: Rigter H, Crabbe JC (eds) Alcohol tolerance and dependence. Elsevier, Amsterdam, pp 1–51Google Scholar
- Engleman EA, McBride WJ, Wilber AA, Shaikh SR, Eha RD, Lumeng L, Li TK, Murphy JM (2000) Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats: effects on dialysate dopamine levels and ethanol intake. Alcohol Clin Exp Res 24:795–801PubMedCrossRefGoogle Scholar
- Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R, Kampf P, Stracke R, Baehr M, Naber D, Wiedemann K (2003) Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch Gen Psychiatry 60:92–99PubMedCrossRefGoogle Scholar
- McClearn G, Rodgers D (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:691–695Google Scholar
- Murphy JM, McBride WJ, Lumeng L, Li TK (1988) Effects of serotonin and sopamine agents on ethanol intake of alcohol-preferring P rats. Alcohol Clin Exp Res 12:306AGoogle Scholar