Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation
[Technical Report, Annual Report]
ALBERT EINSTEIN COLLEGE OF MEDICINE BRONX NY
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Antipsychotic drugs APDs are widely used psychotropic medications, though they have significant metabolic side effects. While the mechanisms for these metabolic disturbances are poorly understood, the single known unifying property of all APDs is their blockade of the dopamine D2 D2R and D3 D3R receptors. We therefore hypothesize that D2R andorD3R mediate the metabolic side effects of APDs both centrally in the hypothalamus and peripherally in pancreas, areas critical for metabolic regulation. We had completed the design of a novel inducible D3R-flox mouse in order to selectively knock out expression of D3R in the hypothalamus and pancreatic beta cells, but had lost them due to Covid. We are reconstituting them now. We did not identify major metabolic deficits in central neuronal Nkx 2.1 D3R, D2R, or D3R D2R knockouts relative to their respective controls. We are currently evaluating metabolic and glucose homeostasis phenotypes following Olanzapine and Bromocriptine treatment in HFD mice.
- Medicine and Medical Research