Grant: Project Grant

Antipsychotic drugs are used to treat a number of conditions including schizophrenia, anxiety and bipolar disorders and their use has increased dramatically over the past decade. Unfortunately, these drugs have harmful metabolic side effects such as weight gain and rapid increases in blood sugar with each dose of drug. Together these effects increase the risk for developing type 2 diabetes and cardiovascular disease. In recent work, we have shown that a single session of exercise prior to treatment with antipsychotics completely protected against the acute increase in blood sugar. Although exercise adherence is poor in individuals taking anti-psychotic drugs we have been using exercise as a model to identify pathways which could be targeted to reduce the metabolic side effects of these drugs. Based on preliminary data from our laboratory we have shown that the activation of an energy-sensing enzyme called AMPK confers the same protection against anti-psychotic metabolic side effects as exercise. The purpose of this project is to examine the effects of AMPK in protecting against the acute and long-term metabolic side effects of antipsychotic drugs and to determine if AMPK mediates the beneficial effects of exercise. The data generated from these studies will provide insight into new approaches that could be used to lessen the metabolic consequences of antipsychotic drugs and could shed insight into the mechanisms mediating the protective effects of exercise.