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.

JOHNSON, Z.V., A.A. REVIS, M.A. BURDICK, AND J.S. RHODES. A similar pattern of neuronal Fos activation in 10 brain regions following exposure to reward-or aversion-associated contextual cues in mice. PHYSIOL BEHAV 00(0) 000-000, 2009 -Relapse triggered by drug-paired cues is a major obstacle for successful treatment of drug abuse. Patterns of brain activation induced by drugpaired cues have been identified in human and animal models, but lack of specificity poses a serious problem for craving or relapse interpretations. The goal of this study was to compare brain responses to contextual cues paired with a rewarding versus an aversive stimulus in a mouse model to test the hypothesis that different patterns of brain activation can be detected. Mice were trained to associate a common environmental context with an intraperitoneal injection of saline, lithium choride or cocaine. After measuring each animal for conditioned place preference or aversion, mice were reexposed to the context (CS+ or CS−) in absence of the reinforcer to analyze patterns of Fos expression in 10 brain regions chosen from previous literature. Levels of Fos in the cingulate cortex, paraventricular thalamic nucleus, paraventricular hypothalamic nucleus, and dentate gyrus differed in CS+ versus CS− groups, but the direction of the differences were the same for both lithium chloride (LiCl) and cocaine reinforcers. In the cingulate cortex, Fos was positively correlated with degree of place preference for cocaine or aversion to LiCl whereas in the periaqueductal gray the relationship was positive for LiCl and negative for cocaine. Results confirm Fos responses to reward-or aversionpaired cues are similar but specificity is detectable. Future studies are needed to comprehensively establish neuroanatomical specificity in conditioned responses to drugs as compared to other reinforcers.