Effect of flumazenil on memory retrieval determined by trial-to-criteria inhibitory avoidance method in mice

In India, the incidence of Alzheimer’s disease (AD) is substantial and is approximately 14 times higher among persons older than 85 years compared with those between 65 and 69 years of age. In a study conducted in Southern India, incidence of AD was found to be 11.67% in 55 years and above age group and 15.54% in 65 years and above age group. Currently approved drugs in the treatment of AD act on cholinergic system (e.g. donepezil) and glutamatergic system (e.g., memantine). Treatment of AD till date is far from satisfactory. Recent failures of several phase III trials of many potential drug molecules for the treatment of AD have reiterated the need to find new molecular targets. In addition, the role of other neurological mechanisms, for example, gamma-aminobutyric acid (GABA)-ergic system as a potential target for the treatment of AD has not been explored in details. Benzodiazepines are the drugs that selectively bind to modulatory site of GABAA receptor. This modulatory site is different from GABA binding site and is specific for benzodiazepines. The discovery of specific benzodiazepine receptors in the central nervous system of higher vertebrates led to subsequent identification of possible endogenous effectors (benzodiazepine endocoids or endozepines) for these receptors. A study done by Kumar et al. has shown that CGS 8216, a benzodiazepine receptor antagonist, enhances learning and memory in mice by inhibiting the action of endozepines. Flumazenil is a benzodiazepine receptor antagonist. It is used to reverse the adverse psychomotor, amnestic, and sedative effects of benzodiazepine receptor agonists. Flumazenil has also been found to accelerate acquisition, improve retention, and protect against experimental amnesia in mice. In AD, the defect in memory retrieval is associated with long-term memory loss. Previously, effects of flumazenil in memory acquisition have been studied, but its effect on memory retrieval is yet to be explored. Hence, this study was planned to evaluate the effect of flumazenil on memory retrieval in mice.