Atypical
antipsychotics are associated with increased risk of
weight gain, and researchers have turned to rodent models to better understand underlying mechanisms.
Weight gain has been inconsistent in these studies though, possibly related to the rapid metabolism of
antipsychotics in rodents. This study investigates
olanzapine, an atypical
antipsychotic with high liability for
weight gain in humans, administered to rats by continuous infusion via osmotic minipump versus daily subcutaneous (s.c.) or intraperitoneal (i.p.)
injections. We examined
body weight, food intake and body composition for
olanzapine (7.5mg/kg/day) versus placebo (n=8/group) in female Sprague-Dawley rats using the 3 routes of administration over 14 days. For
olanzapine treated animals,
weight gain was significantly greater in the minipump sample compared to both s.c. and i.p.
injections. Twice as many animals (i.e. 75%) gained ≥ 7%
body weight compared to either daily s.c. or i.p.
injections.
Olanzapine treated animals consumed more kilocalories than vehicle, and the minipump group consumed more than either daily injection group, although the difference with the s.c. sample was nonsignificant. Significantly more visceral fat was amassed in
olanzapine treated animals versus vehicle, again greatest in the minipump sample, although differences between groups did not reach significance. The magnitude of increase across all groups fits with other evidence suggesting change in body composition may represent a more sensitive measure than
body weight in assessing
antipsychotic related changes. We conclude that the rodent model is tenable in evaluating the effects of
antipsychotics on
weight/body composition.