A. Akubuiro, M. Bridget Zimmerman, L. L. Boles Ponto, S. A. Walsh, J. Sunderland, L. McCormick and M. Singh Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice Genes, Brain and Behavior 12
We find ADAR2 transgenic mice display a preference for diets with high fat content and their overeating is non-distractible and goal-oriented toward food. The exploratory PET imaging finds higher glucose metabolism in the hypothalamus, right hippocampus and mid brain region and a trend toward higher metabolism in the striatum. Dysregualted ADAR2 protein expression and altered 5HT2CR splice variants, dopamine and opioid receptor expression in the hypothalamus suggests ADAR2 plays an important role in feeding and reward behaviors of ADAR2 transgenic mice. Dysfunctional reward circuitry is associated with significantly altered mu, D1 and D2 receptors mRNAs in hypothalamus and increased D1 receptor mRNA expression and altered bioamines in striatum of ADAR2 transgenic mice. Significant changes in serotonin and dopamine metabolites in the striatum further suggests a dysfunctional reward system involving both ‘liking’ and ‘wanting’ behaviors, which most likely contributes to the incentive overeating behavior of ADAR2 transgenic mice.
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