Peripheral Injection Of Risperidone, An Atypical Antipsychotic, Alters The Body Weight Gains Of Rats

Ota et al . 1 recently addressed the important issue of developing an animal (rat) model of weight gain induced by novel ‘atypical’ antipsychotics Their study involved risperidone, which is known to induce weight gain in humans. 2 Most, but not all, novel antipsychotics induce weight gain, 3 although the weight gain induced by risperidone in humans is smaller in magnitude that that induced by olanzapine. 4 Olanzapine-induced weight gain has recently been modelled by us in rats 5 and it would be a considerable advantage for work in this area if risperidone-induced weight gain was also modelled effectively in rodents. Novel antipsychotic-induced weight gain has very serious clinical implications, being associated with enhanced morbidity and mortality, as well as reduced compliance. 6 However, the causes of the weight gain induced by many novel antipsychotics remain enigmatic. Many of the wide range of receptors at which novel antipsychotics act are implicated in the control of food intake (e.g. -adrenoceptors, various serotonergic and dopaminergic receptors and histamine H 1 receptors). However, it has, to date, proved impossible, on the basis of clinical studies, to determine the role of any one such receptor in antipsychotic-induced weight gain. 7 It is well documented that the weight gain induced by novel antipsychotics is associated with abnormalities in various hormonal systems, including leptin, 8 insulin 9 and prolactin. 7 Thus, it seems most likely that the development of animal models of novel antipsychotic-induced weight gain in which measures of food intake and bodyweight are supplemented by metabolic and endocrine measures, exactly as in the study by Ota et al ., 1 will prove a very powerful approach with which to advance this field. Indeed, in a recent major review of this area, Baptista et al . 7 highlighted the need to develop such models as a primary current ‘research perspective’. Thus, the type of empirical research reported by Ota et al . 1 is to be highly commended. It is, however, regrettable that examination of the work reported by Ota et al . 1 suggests that the conclusions they have drawn from their data relating to bodyweight and food intake are not supported by the statistical analysis presented and, thus, attempts to relate these findings to metabolic and endocrinological measures may be invalid. In their study, they administered risperidone for 21 days to four groups of rats treated with either vehicle or one of three doses of risperidone. Bodyweights and food intake were recorded daily. These data are reported as being analysed by repeated-measures