Article

Risperidone alters food intake, core body temperature, and locomotor activity in mice

Department of Biostatistics, University of Alabama at Birmingham, United States
Physiology & Behavior (Impact Factor: 3.03). 03/2009; 96(3):457-463. DOI: 10.1016/j.physbeh.2008.11.011

ABSTRACT Risperidone induces significant weight gain in female mice; however, the underlying mechanisms related to this effect are unknown. We investigated the effects of risperidone on locomotor activity, core body temperature, and uncoupling protein (UCP) and hypothalamic orexin mRNA expression. Female C57BL/6J mice were acclimated to individual housing and randomly assigned to either risperidone (4 mg/kg BW day) or placebo (PLA). Activity and body temperature were measured over 48-hour periods twice a week for 3 weeks. Food intake and body weights were measured weekly. UCP1 (BAT), UCP3 (gastrocnemius), and orexin (hypothalamus) mRNA expressions were measured using RT-PCR. Risperidone-treated mice consumed more food (p = 0.050) and gained more weight (p = 0.0001) than PLA-treated mice after 3 weeks. During the initial 2 days of treatment, there was an acute effect of treatment on activity (p = 0.046), but not body temperature (p = 0.290). During 3 weeks of treatment, average core body temperatures were higher in risperidone-treated mice compared to controls during the light phase (p = 0.0001), and tended to be higher during the dark phase (p = 0.057). Risperidone-treated mice exhibited lower activity levels than controls during the dark phase (p = 0.006); there were no differences in activity during the light phase (p = 0.47). UCP1 (p < 0.01) and UCP3 (p < 0.05) mRNA expressions were greater in risperidone-treated mice compared to controls, whereas, orexin mRNA expression was lower in risperidone-treated mice (p < 0.01). These results suggest that risperidone-induced weight gain in mice is a consequence of increased energy intake and reduced activity, while the elevation in body temperature may be a result of thermogenic effect of food intake and elevated UCP1, UCP3, and a reduced hypothalamic orexin expression.

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    • "A number of studies have also indicated that risperidone administration in rats through different routes increased food intake and body weight in a four-week period (Baptista et al., 2002; Ota et al., 2002, Cope et al., 2005; Pouzet et al., 2003; Davoodi et al., 2009). Previous studies have found that animals in the risperidone group consumed more food compared to the vehicle group, which may have caused increased adipose tissue mass and subsequent obesity (Cope et al., 2009). In addition, plasma leptin levels increased in the risperidone group compared with the vehicle group. "
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    • "Limitations of the present study include any psychotropic medication administered, but elevations of hcrt-1 are only reported for sertraline and risperidone, which we've prescribed each in one patient (Salomon et al., 2003; Cope et al., 2009). Furthermore, the design of the study did not consider the locomotor activity prior to lumbar puncture. "
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