Effects of flumazenil and naloxone on scopolamine-induced impairment of spatial working memory in rats

Objective To investigate the effects of flumazenil and naloxone on scopolamine-induced impairment of spatial working memory in rats.Methods Forty pathogen-free SD rats weighing 160-200 g were randomly divided into 4 groups(n=10 each):group I control(group C);group IIscopolamine(group S);group III flumazenil+scopolamine(group SF)and group IV naloxone+scopolamine(group SN).Scopolamine 0.8 mg/kg was administered IP once a day for 3 consecutive days in group II-IV.In group SF and SN flumazenil 0.5 mg/kg and naloxone 2 mg/kg were administered IP respectively once a day for 3 consecutive days in addition to scopolamine.Thirty minutes after last IP administration,cognitive function was assessed using Y-maze.The animals were killed after cognitive function assessment and bilateral hippocampi Were isolated for determination of mAChRM1 mRNA expression(by RT-PCR)and detection of ChAT positive neurons(by immuno-histochemistry).Results Cognitive dysfunction developed in group S as compared with control group and was ameliorated in group SF and SN.The number of ChAT positive neurong and mAChRM1 mRNA expression were significantly decreased in group S compared with control group and were significantly higher in group SF and SN than in group S.Conclusion Flumazenll and naloxone can ameliorate the scopolamine-induced impairment of spatial working memory by improving cholinergic neuron function. Key words: Flumazenil; Naloxone; Scopolamine; Hippoeampus; Cognition disorders