CHRONIC ADMINISTRATION OF RISPERIDONE DOES NOT SIGNIFICANTLY INCREASE FosB ACTIVITY IN THE RAT BRAIN. K. H. Martines, C. T. McNutt, J. C. Gowdy, N.M. Lee, M. E. Bardgett. Program No. 956.17. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.

    Risperidone is a second generation antipsychotic drug that has shown some cognitive enhancing properties in people with schizophrenia, combined with a reduced risk of extrapyramidal side-effects.  Some suggest that the clinical effects of antipsychotic drugs are partly mediated by regulation of immediate early genes from the Fos family of transcription factors.  While studies have shown that acute administration of high doses of risperidone increases Fos expression in certain brain regions, including the nucleus accumbens (NAc), dorsolateral striatum (CPu) and medial prefrontal cortex (PFC), few have examined the effects of chronic risperidone treatment on FosB activity.  The purpose of this study was to examine the effects of chronic risperidone administration (0.25 mg/kg/day for 42 days) on FosB activity in neurons of the NAc shell and core (NAcSh and NAcC, respectively), PFC, entorhinal cortex (EtC), and the dorsal and medial striatum (CPuD and CPuM, respectively). FosB activity was measured using immunohistochemical analysis of FosB-stained neurons.  While there were statistical trends in the NAcC and CPuD, the number of FosB positive neurons following chronic risperidone treatment was not significantly elevated in any of the brain regions measured.  The lack of elevated FosB activity observed after chronic risperidone treatment is similar to the effects of chronic clozapine and is in contrast to the elevated effects of haloperidol on FosB activity.  This work provides further support for the atypical classification of risperidone.  This research was supported by the NKU Center for Integrative Natural Science and Mathematics and the NIH Kentucky Biomedical Research Infrastructure Network.

RISPERIDONE IMPROVES SPATIAL WORKING MEMORY DEFICITS AND NORMALIZES ACTIVITY IN RATS WITH HIPPOCAMPAL DAMAGE.  M. E. Bardgett, C. T. McNutt, J. C. Gowdy, N.M. Lee, K. H. Martines.  Program No. 344.8. 2003 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2003. Online.  

    Reduced hippocampal volume has been reported in many neuropsychiatric disorders and, given the role of the hippocampus in memory, may give rise to cognitive deficits associated with these disorders. Animal models of hippocampal damage may be useful in identifying treatments that specifically target behavioral disturbances linked to reduced hippocampal volume. Risperidone is an atypical antipsychotic drug that has shown some cognitive enhancing properties in people with schizophrenia. We report here that daily treatment with risperidone produces a modest yet significant memory improvement in rats with hippocampal damage. Adult male rats with or without NMDA lesions of the dorsal hippocampus were given daily injections of either saline or 0.25 mg/kg of risperidone beginning one week after lesion surgery. At two weeks post-surgery, rats with hippocampal damage were found to be more active than control animals, and risperidone treatment fully reversed this effect. At three and four weeks post-surgery, all rats were tested in a food-motivated, delayed spatial alternation paradigm. While saline-treated rats with hippocampal damage alternated at chance levels, the risperidone-treated rats with hippocampal damage performed the task slightly but significantly better. These data suggest that behavioral disturbances linked to reduced hippocampal volume in neuropsychiatric disorders may be sensitive to risperidone. Future work should assess where and how risperidone works in the brain to produce these positive effects on behavior.
Support Contributed By: the NKU Center for Integrated Natural Sciences and Mathematics and the NIH-Kentucky Biomedical Research Infrastructure Network.