Cognitive profile of reserpine following its repeated administration in rats: a progressive model of memory impairment

Abstract Contrary to other animal models for Alzheimer’s disease (AD) and related cognitive deficits involving acute memory impairment, the present study was designed to provide an animal model exhibiting a progressive decrease in memory upon repeated administration of reserpine (0.1 mg/kg). In the present study, reserpine was injected daily (once a day for three weeks). Short- and long-term memories were assessed using a Morris water maze on a weekly basis. A 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 -70°C. Impairment of short- and long-term activities (as monitored in the Morris water maze) was not observed until after the first week. Long-term memory was found to be impaired earlier than short-term memory. The novel object recognition test also revealed reserpine-induced impairment of working memory. Neurochemical analysis of the whole brain samples by HPLC-EC showed that repeated administration of reserpine significantly decreased dopamine (p < 0.01), HVA (homovaluronic acid) (p < 0.05) and 5-HIAA (5-hydroxyindol acetic acid) (p < 0.01) levels. This further confirmed that these neurochemical deficits are the underlying reason for memory impairment. The present study provides evidence that repeated administration of reserpine can be used as a ‘progressive’ animal model of memory impairment. The results could be beneficial for understanding the pathophysiology of Parkinson’s-related memory impairment.