Varenicline ameliorates learning and memory deficits in amyloid β(25-35) rat model of Alzheimer s disease

Introduction: Alzheimer s disease (AD) is a enfeeble neurodegenerative disorder characterized by increased β-amyloid (Aβ) 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. Methods: In the present study, effects of the intracerebroventricularly administration of an agonist of nicotinic cholinergic receptors, varenicline(0.5 and 2 μg/μl), on learning and memory impairments induced by intrahippocampal Aβ(25-35) injection was assessed in rats. Results: The results showed that the intrahippocampal Aβ(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). Discussion: This study indicates that varenicline pretreatment attenuates Aβ- induced impairment of short-term spatial memory in rats probably due to its agonist activity at nicotinic receptors.