Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation
Abstract
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 and/or D3R 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 did not identify major metabolic deficits in central neuronal Nkx 2.1 D3R, D2R, or D3/R D2R knockouts relative to their respective controls. We have evaluated metabolic and glucose homeostasis phenotypes following Domparidone, Bromocriptine an Olanzapine treatment in HFD mice, and found that Bromocriptine is ineffective while Olanzapine has mild and variable beneficial effects on glucose homeostasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2022
- Accession Number
- AD1223919
Entities
People
- Despoina Aslanoglou
- Gary J Schwartz
- Zachary Freyberg
Organizations
- Albert Einstein College of Medicine