Effect of dizocilpine (MK-801) on the working memory of rats on a three-panel runway apparatus

ABSTRACT

Background: Understanding the processes underlying cognitive functions is a prerequisite to develop strategies for the treatment of cognitive deficits. There is a great need for valid animal models for investigating the cognitive enhancing effects of potential therapeutics. Many studies have investigated animal models of cognitive deficits by using animals treated with compounds that compromise cognitive abilities. Glutamate, an excitatory neurotransmitter and abundantly distributed in the central nervous system is involved in memory processes through N-methyl-d-aspartate (NMDA) receptors. The behavioural consequences of blocking the NMDA receptor provide the rationale for cognitive impairment as an animal model for the cognitive deficits associated with dementia. Authors investigated the effect of dizocilpine (MK-801), an NMDA-receptor antagonist (non-competitive) on the working memory in rats using the three-panel runway apparatus.Methods: Total 24 trained male albino rats were randomly divided into 4 groups of 6 animals each. Varying doses of MK-801 were administered to the animals. Working memory errors and latency periods were evaluated on the three panel Runway apparatus.Results: Treatment with MK-801 at the dose of 0.03mg/ kg did not result in any significant change in working memory errors or latency period in comparison to saline control. MK-801 treatment at dose of 0.1mg/kg and 0.3mg/kg resulted in a significant increase in the number of working memory errors and latency period as compared to control.Conclusions: Authors conclude that MK-801 treatment in the dose of 0.1mg/ kg and 0.3mg/kg resulted in working memory deficits on the three-panel runway apparatus. Rats with cognitive deficits induced by the prototypical N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 may provide a relevant animal model of dementia based on the mechanistic approach of blocking NMDA/glutamatergic signalling.