RSA 2007 Abstracts

The University of Santa Barbara

ACCUMBENS mGluR5 BLOCKADE REDUCES EXCESSIVE ALCOHOL CONSUMPTION IN MICE: D. K. Cozzoli; S. Goulding; K. K. Szumlinski.
Department of Psychology and the Neuroscience Research Institute, University of California at Santa Barbara, CA, 93106-9660.

            The systemic administration of antagonists at either the mGluR1 or mGluR5 subtypes of Group1 metabotropic glutamate receptors (mGluRs) attenuate various aspects of alcohol reward in the alcohol-preferring C57BL/6J mouse. The present study extends these earlier data by examining the effect of local infusion of the mGluR1 antagonist CPCCOEt (1, 3 ug) and the mGluR5 antagonist MPEP (0.1, 0.3, 1.0 ug) into the nucleus accumbens upon excessive alcohol intake. High consumption of alcohol was established by utilization of the SHAC (Scheduled High Alcohol Consumption) model where mice were presented with a single bottle containing 5% alcohol for a 30 minute period at 3 hours after the onset of the dark cycle, followed by access to the home cage bottle for a total of 10 hours of fluid availability. The alcohol bottle was presented every third day and intra-accumbens infusions of antagonists occurred immediately prior to bottle presentation. An intra-accumbens infusion of MPEP dose dependently reduced alcohol consumption with the highest dose reducing alcohol intake by 50%. The attenuating effects of MPEP appear to be specific to alcohol as 1.0 ug of MPEP did not reduce water intake. In contrast to MPEP, CPCCOEt intra-accumbens infusion failed to reduce excessive alcohol consumption. Consistent with the results of earlier microinjection studies of cocaine self-administration, these data indicate an important role for the function of mGluR5 but not mGluR1 in regulating excessive alcohol intake and implicate mGluR5-mediated intracellular signaling cascades in the neurobiology of alcoholism.
This work was supported by NIAAA grant Developmental U01 AA-016650 (INIA-West) to KKS.