Acute effects of antipsychotic drugs on metabolic indices in a rodent model

Abstract

BACKGROUND: Recent studies indicate that treatment with atypical antipsychotic drugs represents a major risk factor for metabolic syndrome. Side-effects of these drugs include weight gain, hyperlipidemia, glucose intolerance and insulin resistance. The objective of this study is to examine these metabolic abnormalities through the use of a rodent model.  METHODS: Adult female Sprague-Dawley rats were treated acutely with either a low or high dose of clozapine (2, 20 mg/kg) olanzapine (1.5, 15 mg/kg), risperidone (0.5, 2.5 mg/kg), haloperidol (0.1, 1.0 mg/kg) or vehicle. Separate cohorts of rats were subjected to an intraperitoneal glucose tolerance test (IGTT) at 1, 3 and 6 hours after drug treatment. Blood samples were drawn every 15 min for a two hour period.  RESULTS: For all four antipsychotics, the high dose produced strong glucose intolerance, but this effect was only evident at the low dose with the atypical drugs. Effects were greatest one hour after drug administration and diminished over time. CONCLUSIONS: These data show that, in an animal model, atypical drugs with well known metabolic side-effects (clozapine and olanzapine), more modest metabolic side-effects (risperidone) and even a typical antipsychotic can all cause glucose intolerance with an acute, high dose. Furthermore, metabolic effects are both dose and time dependent