Chronic administration of olanzapine affects Behavioral Satiety Sequence and feeding behavior in female mice

The aim of the study was to assess the effects of chronic olanzapine (Ola) administration on feeding behavior. Although atypical antipsychotics (AAPs) have greatly improved the management of schizophrenia and extrapyramidal symptoms, substantial bodies of literature point out that most of these agents are highly related to a major risk of metabolic drawbacks, leading to dyslipidemia and obesity. Among these compounds, Ola is one of the more weight gain-inducing AAPs. In the present study, we analyzed the Behavioral Satiety Sequence (BSS) in female mice given a palatable diet (wet mash) and chronically administered Ola (0.75, 1.5, 3 mg/kg per os) for 36 days. The results showed that administration of the highest dose of Ola postponed the onset of satiation, as suggested by the rightward shift of the BSS. This effect was confirmed by an increase in the actual food intake by the Ola (3 mg/kg) mice. These results suggest that one of the possible mechanisms involved in AAP-induced weight gain is alteration of the hunger-satiety regulation in female mice. These findings are consistent with the hypothesis that enhanced food intake and diminished central sensitivity to satiation signaling may cooperate in promoting weight gain and metabolic dysregulation in rodents and patients taking antipsychotic medications.