The Effects of Acute Olanzapine Exposure on Central Leptin Mediated Regulation of Energy Homeostasis and Food Intake

Second-generation antipsychotic (SGAs) use is associated with severe metabolic side-effects which may be due to disrupted actions of leptin in the brain. We investigated the ability of olanzapine, a widely used SGA, to impair hypothalamic-leptin-mediated regulation of energy homeostasis and food intake. Healthy, male, Sprague Dawley rats received an acute intracerebroventricular (ICV) infusion of leptin or vehicle along with an acute peripheral injection of olanzapine or vehicle at the beginning of 12-h light and dark cycles. Changes in metabolic parameters were recorded using indirect calorimetry cages over 24 hours. Glucose tolerance was assessed using IPGTTs. Treatment with leptin and olanzapine, alone or in combination, reduced respiratory exchange ratio (RER) in light and dark cycles. ICV-leptin reduced dark-cycle food intake regardless of olanzapine treatment. Furthermore, treatment with olanzapine resulted in disturbed glucose tolerance. Olanzapine-induced dysglycemia appeared to be independent of hypothalamic leptin action, and ICV-leptin did not alleviate olanzapine-induced glucose intolerance.M.Sc