Methylcobalmine (V-B12) increases cerebral acetylcholine levels and improves passive avoidance response in stroke-prone spontaneously hypertensive rats

Mental deterioration in Alzheimer-type dementia has been known to be associated with cerebral vitamin B 12 (V-B 12 ) deficiency. We have recently shown that inferior performance in passive avoidance is accompanied with hippocampal cholinergic dysfunction in stroke-prone spontaneously hypertensive rats (SHRSP), an animal model of vascular dementia, as compared with normotensive control Wistar Kyoto rats (WKY). Behavioral impairment in the passive avoidance task was also observed in SHRSP with positive correlations between hippocampal acetylcholine (ACh) levels and latency of the passive avoidance response. In this study, we examined the effects of methylcobalmine on cerebral ACh levels and passive avoidance response in SHRSP. Chronic (14 weeks) oral administration of methylcobalmine significantly improved inferior learning performance in passive avoidance response compared with that observed in control SHRSP. Furthermore, cerebral ACh levels correlated positively with the total response latency in passive avoidance task. These findings suggest that both V-B 12 and cholinergic deficiencies might be involved in the mechanisms underlying the pathogenesis of dementia. Methylcobalmine may be beneficial in the treatment of dementia with ACh deficiencies.