In a recent double-blind placebo-controlled study we found the broad spectrum anticonvulsant zonisamide (ZON) to have effects on ethanol consumption that are comparable to those of topiramate. We hypothesize here that the administration of ZON, by attenuating the hyperexcitability of the brain during periods of abstinence, through its neuro-protective effects, and its enhancement of dopamine activity in midbrain and frontal regions will counteract the effects of alcohol that lead to impaired regulatio of emotional and reward processes that control the consumption of alcohol. This will be evident by the normalization of brain activity seen in performance of the alcohol and emotional-word Stroop tasks and in a reduction of the BOLD response to alcohol related images. The results of this study should provide an indication of the neurobehavioral mechanisms through which ZON may act to regulate the consumption of alcohol.
The proposed research is relevant to the public health mission of NIAAA because it will use new methods of developing new medications for alcoholism treatment by identifying how zonisamide effects brain circuits regulatory alcohol intake and reward. Alcoholism is the third leading cause of preventable death in the US, with 80,000 deaths annually.
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