N-methyl-D-aspartate Receptors Are Involved in Caffeine-Induced Facilitation on Memory Retention of Passive Avoidance Learning in Rats

Abstract

Background: Caffeine is an antagonist of adenosine receptors. It preserves cognition and reduces neurodegeneration. The MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has also shown amnesic properties in animal models. The effect of caffeine on MK-801-induced amnesia has not been the subject of any recent study. Methods: In this study, the effects of different doses (10 and 30 mg/kg) of caffeine on Wistar male rats (eight in each group), passive-avoidance (PA) response, and the impairment of this response by the NMDA receptor antagonist MK-801 (dizocilpine) were evaluated. The PA response was examined by measuring the step-through latency, 1 and 3 days after the animals received foot-shock training. Results: When given intraperitoneally before the training session, 10 mg/kg caffeine elongated the PA response, but 30 mg/kg did not, and it even reduced the step-through latency significantly. Before and after training, administration of 0.2 mg/kg MK-801 significantly elongated the PA response. This finding showed that MK-801 had a detrimental effect on learning, consolidation, and memory. We found the first evidence that pre-training and pre-testing administration of 10 mg/kg caffeine significantly reversed the learning and memory consolidation process disrupted by MK-801. Conclusion: These results show an interaction between caffeine and the glutamatergic system, suggesting that low-dose caffeine can prevent learning deficit and amnesia produced by a NMDA antagonist in rats (model of schizophrenia in human) when injected in pre- and post-training phase and may be clinically useful for treating cognitive impairments in schizophrenia.