Acute effects of acamprosate and MPEP on ethanol Drinking-in-the-Dark in male C57BL/6J mice.
BACKGROUND
Recently, a simple procedure in mice, Drinking-in-the-Dark (DID), was hypothesized to have value for medication development for human alcoholism. In DID, mice are offered intermittent, limited access to ethanol over a series of days during the dark phase that results in rapid drinking to intoxication in predisposed genotypes.


METHODS
We measured the effects of acamprosate or MPEP, metabotropic glutamate 5 receptor (mGluR5) antagonist, on intake of 20% ethanol, plain tap water or 10% sugar water using the DID procedure in male C57BL/6J mice.


RESULTS
Acamprosate (100, 200, 300, or 400 mg/kg) dose dependently decreased ethanol drinking with 300 mg/kg reducing ethanol intake by approximately 20% without affecting intake of plain water or 10% sugar water. MPEP (1, 3, 5, 10, 20, or 40 mg/kg) was more potent than acamprosate with 20 mg/kg reducing ethanol intake by approximately 20% and for longer duration without affecting intake of plain water or 10% sugar water.


CONCLUSIONS
These results support the hypothesis that mGluR5 signaling plays a role in excessive ethanol intake in DID and suggest DID may have value for screening novel compounds that reduce overactive glutamate signaling for potential pharmaceutical treatment of excessive ethanol drinking behavior.
Gupta
Tripta
T
Department of Psychology, The Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Syed
Yaqoob M
YM
Revis
Andrew A
AA
Miller
Samantha A
SA
Martinez
Marina
M
Cohn
Kellen A
KA
Demeyer
Michael R
MR
Patel
Kevin Y
KY
Brzezinska
Weronika J
WJ
Rhodes
Justin S
JS
D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology*; D000437:Alcoholism / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D003624:Darkness; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000627:therapeutic use*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000427:Alcohol Deterrents; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; D013654:Taurine; C121465:6-methyl-2-(phenylethynyl)pyridine; D000077443:Acamprosate