The effects of fluoxetine on cognitive functions in animal model of Alzheimer's disease.

Cognitive impairment is the hallmark of progressive neurodegenerative process observed in Alzheimer's disease (AD). Acetylcholine (Ach) deficiency is considered to be one of major factors underlying cognitive dysfunction in AD. Several lines of evidence suggest that sigma receptor ligands can elevate Ach extracellular levels in prefrontal cortex rat brain. Since all selective serotonin reuptake inhibitors (SSRIs) show affinity for sigma receptors, it has been assumed that fluoxetine could improve cognition in AD. The aim of study was to investigate the effects of fluoxetine on learning and memory processes in experimental model of AD in rats. Experiments were carried out on adult male Wistar rats divided into three major groups: intact control, sham-operated and nucleus basalis-lesioned rats. Bilateral electrolytic lesions of nucleus basalis Meynert (NBM) (experimental model of AD) were made by 1 mA direct current passed through unipolar electrode for 30 sec. The behavioural test (active avoidance) was performed after recovery period of 10 days from the lesion. The effects of several doses of fluoxetine (3, 5 and 10 mg/kg) on these processes were investigated after 7 days of administration. The results showed that lesion of NBM in rats markedly impaired learning and memory processes compared with controls (intact and sham). Fluoxetine in 5 mg/kg daily doses significantly improved (p<0.05) these processes in lesioned animals. These findings suggest that fluoxetine could be useful as symptomatic therapy in the treatment of AD.