Varenicline ameliorates learning and memory deficits in amyloid beta[25-35] rat model of Alzheimer's Disease

ABSTRACT

Alzheimer's disease [AD] is a enfeeble neurodegenerative disorder characterized by increased beta-amyloid [Abeta] deposition and neuronal dysfunction leading to impaired learning and recall. Among proposed risk factors, impaired cholinergic transmission is a main cause for incidence of disease. In the present study, effects of the intracerebroventricularly administration of an agonist of nicotinic cholinergic receptors, varenicline[0.5 and 2 microg/microl], on learning and memory impairments induced by intrahippocampal Abeta[25-35] injection was assessed in rats. The results showed that the intrahippocampal Abeta[25-35] injected rats exhibit lower spontaneous alternation score inY-maze tasks [p<0.05], impaired retention and recall capability in the passive avoidance test [p<0.05], and fewer correct choices [p<0.001] and more errors[p<0.001] in the RAM task. Varenicline, almost in both doses, significantly improved alternation score in Y-maze task [p<0.001], impaired retention and recall capability in the passive avoidance test [p<0.05], and correct choices in the RAM task [p<0.001]. This study indicates that varenicline pretreatment attenuates Abeta- induced impairment of short-term spatial memory in rats probably due to its agonist activity at nicotinic receptors.