Arginine vasopressin prevents against Aβ25–35-induced impairment of spatial learning and memory in rats

Amyloid β protein (Aβ) is thought to be responsible for loss of memory in Alzheimer's disease (AD). A significant decrease in [Arg8]-vasopressin (AVP) has been found in the AD brain and in plasma; however, it is unclear whether this decrease in AVP is involved in Aβ-induced impairment of spatial cognition and whether AVP can protect against Aβ-induced deficits in cognitive function. The present study examined the effects of intracerebroventricular (i.c.v.) injection of AVP on spatial learning and memory in the Morris water maze test and investigated the potential protective function of AVP against Aβ-induced impairment in spatial cognition. The results were as follows: (1) i.c.v. injection of 25 nmol Aβ25–35 resulted in a significant decline in spatial learning and memory; (2) 1 nmol and 10 nmol, but not 0.1 nmol, AVP injections markedly improved learning and memory; (3) pretreatment with 1 nmol or 10 nmol, but not 0.1 nmol, AVP effectively reversed the impairment in spatial learning and memory induced by Aβ25–35; and (4) none of the drugs, including Aβ25–35 and different concentrations of AVP, affected the vision or swimming speed of the rats. These results indicate that Aβ25–35 could significantly impair spatial learning and memory in rats, and pretreatment with AVP centrally can enhance spatial learning and effectively prevent the behavioral impairment induced by neurotoxic Aβ25–35. Thus, the present study provides further insight into the mechanisms by which Aβ impairs spatial learning and memory, suggesting that up-regulation of central AVP might be beneficial in the prevention and treatment of AD.