Acute effects of naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice.
BACKGROUND
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.


OBJECTIVE
To determine whether the model displays predictive validity with naltrexone, and whether opioid or dopaminergic mechanisms mediate excessive drinking in the model.


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.


RESULTS
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.


CONCLUSIONS
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.
Kamdar
N K
NK
Department of Psychology, Beckman Institute, Urbana, IL 61801, USA.
Miller
S A
SA
Syed
Y M
YM
Bhayana
R
R
Gupta
T
T
Rhodes
J S
JS
D000428:Alcohol Drinking; D000435:Alcoholic Intoxication; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003624:Darkness; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015203:Reproducibility of Results; D012646:Self Administration; D015398:Signal Transduction / Q000187:drug effects
D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D010879:Piperazines; D000431:Ethanol; D009271:Naltrexone; C043425:vanoxerine