A similar pattern of neuronal Fos activation in 10 brain regions following exposure to reward- or aversion-associated contextual cues in mice.

Relapse triggered by drug-paired cues is a major obstacle for successful treatment of drug abuse. Patterns of brain activation induced by drug-paired 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 chloride or cocaine. After measuring each animal for conditioned place preference or aversion, mice were re-exposed 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 was 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 aversion-paired 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.

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.