Effects of MK-801 and ketamine on short-term memory deficits in passive avoidance step-down task paradigm in mice

The phenomenon of long-term potentiation (LTP) formation in hippocampal and neocortical brain areas has been suggested as a mechanism for learning and memory where NMDA-receptors play a significant role. Various agonists have been proposed to facilitate LTP and thereby learning and memory. Competitive and non-competitive antagonists of NMDA-receptors block LTP formation and produce attentional or acquisition deficit in animals. A series of experiments were carried out with noncompetitive NMDA antagonists, MK-801 (10-100 micrograms/kg) and ketamine (1-10 mg/kg), in passive avoidance step-down task paradigm in mice. MK-801 showed complete disruption of acquisition at higher doses, while very low doses showed improvement in retention. MK-801 showed additive or potentiating influence on scopolamine-induced deficits. The results of the interaction of NMDA antagonists with scopolamine provide a basis for the speculation that cholinergic- and NMDA-antagonism may play a hand in hand role in short-term memory disturbances in passive avoidance step-down task paradigm in mice.