Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus, and nucleus accumbens in old rats after chronic donepezil administration.

In Alzheimer's disease brains, morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus (VH), and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil-treated rats, a significant increment of the dendritic spines number in pyramidal neurons of the PFC and dorsal hippocampus was observed. However, pyramidal neurons of the VH and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12-month-old rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging.