Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism.
BACKGROUND
The development of mouse models of ethanol consumption and ethanol-seeking behavior is of particular importance in understanding the underlying mechanisms of drug abuse because these models can enable an analysis of an effect of specific genotype on drug-seeking behavior and the interaction of potential therapeutics with genotype. However, there are some limitations with present models, notably the inability to examine appetitive and consummatory behavior separately.


METHODS
In the present study, C57BL/6 mice were trained to self-administer 10% ethanol in a modified operant protocol that allowed a clear delineation of consummatory and appetitive phases. The utility of this procedure was confirmed with the use of the metabotropic glutamate 5 (mGlu5) receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP).


RESULTS
Limited-access consumption during the dark phase of the light-dark cycle with intermittent access (every second or third day) led to a high level of consumption by the mice. MTEP caused a dose-dependent decrease in both the consumption of ethanol and the appetitive response for ethanol. Furthermore, this effect was unrelated to any effect of MTEP on locomotor activity.


CONCLUSIONS
The model provides a useful paradigm for examining both the appetitive and consummatory phases of ethanol consumption in mice; furthermore, the data indicate mGlu5 receptors are involved in both phases.
Cowen
Michael S
MS
Brain Injury and Repair Group, Howard Florey Institute, University of Melbourne, Royal Parade, Parkville, Victoria, Australia.
Krstew
Elena
E
Lawrence
Andrew J
AJ
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects* / Q000502:physiology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012646:Self Administration; D013844:Thiazoles / Q000494:pharmacology*
C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles