Centre for Addiction and Mental Health –

Central insulin to prevent olanzapine-induced adiposity: a rodent model

Atypical antipsychotic (AAP) medications, the mainstay treatment for psychosis and schizophrenia, are defined by weight gain and metabolic problems that likely contribute to a 2-fold increase in cardiovascular (CV) deaths in this population.

Lifestyle interventions often have limited success, and other medical interventions must be considered. Intranasal insulin, comparable to administration into the brain, could represent a new approach for several reasons: a) schizophrenia has been associated with brain abnormalities in insulin signaling, and b) in healthy humans, intranasal insulin is considered safe and is associated with beneficial effects on cognition and weight. Before moving to humans we will use a rat model to look at insulin given directly into the rat brain to see if it can prevent AAP-associated increases in fat, a key risk factor for CV disease. We also propose to clarify mechanisms of AAP-induced disturbances of energy metabolism, examining if central insulin can attenuate disruptions in shared pathways.