Enhancement of hippocampal-dependent spatial memory by Ashwagandha (Withania somnifera) characterized by activation of NMDA receptors against monosodium glutamate-induced neurotoxicity in rats

Background and AimMonosodium glutamate (MSG) is used in food-additives, and the Food and Drug Administration has placed it under intense scrutiny following several reports that it causes glutamate neurotoxicity. Ashwagandha (ASH) roots are traditionally used for memory enhancement. This study aimed to evaluate the nootropic activity of ASH as well as its therapeutic anti-amnesic activity against MSG-induced hippocampal-dependent spatial memory impairment and hippocampal-NMDAR modulation.MethodA total of 36 rats were divided equally into six groups (n = 6 in each group); the rats in the normal and negative groups were administered daily doses of normal saline and MSG (300 mg/kg), respectively, for 21 days. Two nootropic groups were administered ASH at 300 and 500 mg/kg o.p., respectively, for 21 days. Two other treatment groups were administered daily doses of MSG 300 mg/kg o.p. as well as 300 mg/kg and 500 mg/kg o.p. of ASH for 21 days. The rats' spatial memory was assessed for five days using the MWM. Additionally, NMDAR were measured quantitatively by immunohistochemistry.ResultsWe found that the rats in the nootropic groups showed significantly enhanced nootropic activity characterized by improved hippocampal-dependent spatial memory, as well as increases in the level of NMDAR in the Cornu Ammonis 1 region of their hippocampus. Moreover, we elucidated the therapeutic potential of ASH to protect against the depression of spatial memory caused by MSG-induced neurotoxicity.ConclusionFurther, we elucidated a strong correlation between NMDAR-positive cells in the hippocampus and enhancement of spatial learning induced by long-term administration of ASH as well as a strong correlation between NMDAR positive cells in the hippocampus and depression of spatial learning induced by long-term administration of ASH and MSG.