Repeated treatment with a low dose of reserpine as a progressive model of Parkinson's dementia

Abstract

Present study was designed to monitor the cognitive profile of the animals upon repeated administration of reserpine, so as to determine that whether these animals should be used as animal models of Parkinson’s dementia. In the present study, reserpine was injected daily (once a day for three weeks) at the dose of 0.1mg/kg. Short- and long term memories were assessed using a Morris water maze, on weekly basis. Novel object recognition test was performed after completion of the treatment (day 21). Animals were decapitated on day 21 and brain samples were stored at -70ºC until neurochemical analysis by HPLC-EC. Impairment of short- and long term activities (as monitored in Morris water maze) were not observed until after first week. Long term memory was found to be impaired earlier than the short term memory. Novel object recognition test also exhibited reserpine-induced impairment of working memory. Neurochemical analysis of the whole brain samples by HPLC-EC method showed that repeated administration of reserpine significantly increased DOPAC/ DA ratio (p<0.01). While 5-HIAA/ 5-HT ratio was found to be decreased (p<0.05) in reserpine injected animals. This further confirmed that these neurochemical deficits to be the underlying reason in memory impairment. In conclusion, present study provides evidence that repeated administration of reserpine can be used as a ‘progressive’ animal model of Parkinson’s dementia. Results could be beneficial for face validity and screening of the drugs for the treatment of dementia secondary to Parkinson’s and related disorders.