Effects of olanzapine in male rats: enhanced adiposity in the absence of hyperphagia, weight gain or metabolic abnormalities

• Published in: Journal of psychopharmacology (Oxford) 2007-06, Vol.21 (4), p.405-413
• Main Authors: Cooper, G.D., Pickavance, L.C., Wilding, J.P.H., HarroLd, J.A., HaLford, J.C.G., Goudie, A.J.
• Format: Article
• Language: English
• Subjects: Adiponectin; Adiponectin - blood; Adipose tissue; Adipose tissues; Adiposity - drug effects; Animals; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacology; Antipsychotics; Benzodiazepines - adverse effects; Benzodiazepines - pharmacology; Biological and medical sciences; Blood Glucose - analysis; Body weight gain; Causes of; Chemical properties; Complications and side effects; Dose-Response Relationship, Drug; Drinking - drug effects; Drug therapy; Eating - drug effects; Female; Females; Food intake; Gender differences; Hyperphagia; Hyperphagia - chemically induced; Insulin; Insulin - blood; Leptin; Leptin - blood; Male; Males; Medical sciences; Metabolic Diseases - chemically induced; Neuropharmacology; Olanzapine; Pharmacology. Drug treatments; Plasma levels; Prolactin; Prolactin - blood; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Rattus; Rodents; Sex differences; Sex Factors; Testosterone; Testosterone - blood; Water intake; Weight gain; Weight Gain - drug effects; Weight reduction
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881106069637

Many of olanzapine's (OLZ) actions in humans related to weight regulation can be modelled in female rats (Cooper et al., 2005). Such effects include weight gain, hyperphagia, enhanced visceral adiposity and elevated Levels of insulin and adiponectin. As sex differences have been reported in the effects of antipsychotic drugs, including OLZ, in rats, the current study extended our study in female rats by directly comparing the actions of OLZ in maLes using identical methodology. Individually housed male Han Wistar rats were administered OLZ twice daily (i.p.), at 0, 1, 2, and 4 mg/kg over 21 days. Both differences from, and simiLarities to, the data obtained in females were obtained. Males treated with OLZ showed reduced weight gain, enhanced visceral adiposity and reduced Lean muscle mass. There were no accompanying changes in food or water intake. OLZ did not induce changes in plasma Levels of insulin, Leptin or gLucose. Significant elevation of adiponectin was observed. OLZ-treated males dispLayed elevated prolactin and suppressed testosterone. OLZ's effects in humans can very clearly be most validly modelled in female rats, although the cause(s) of the sex difference in OLZ's actions in rats are not clear. However, the finding that significantly enhanced adiposity is seen in both male and female rats, in other animal species (mice and dogs) and in humans suggests that studies in male rats of OLZ's effects may be of value, by highlighting the consistent ability of OLZ to increase visceral adiposity. It is hypothesized that such adiposity is a key, clinically relevant, common component of OLZ's actions which may be, at Least partially, independent of both OLZinduced weight gain and hyperphagia, and which is induced reliably in male and female rats and other animal species. Possible mechanisms involved in the effects reported are discussed.