Streptozotocin-induced diabetes mellitus affects the NMDA receptors: Role of caffeine administration in enhancing learning, memory and locomotor deficits

OBJECTIVE: To investigate the deterioration of the brain functions by diabetes mellitus (DM) and the beneficial effect of caffeine. MATERIALS AND METHODS: First, the component of N-methyl-D-aspartate receptors (NMDA) of the field excitatory postsynaptic potential (fEPSP) were recorded in streptozotocin (STZ)-induced DM and compared with control animals. Later, 40 mice were divided randomly into five groups (8 mice in each): (1) Normal control (Cont), (2) diabetic group (DM), (3) animals pretreated with i.p. caffeine before the induction of DM (Pre Caf), (4) acute caffeine-treated group (Ac Caf), and (5) chronic caffeine group (Ch Caf). Learning and memory were assessed in Morris-Water maze, and motor coordination was tested by rotarod. RESULTS: A significant reduction in the NMDA-component of the fEPSPs responses was recorded in the hippocampus of the diabetic animals. All the DM-groups demonstrated defects in learning and memory tasks; only the Ac Caf group could reverse the deteriorating effect of DM. This group showed a significantly lower latency values to reach their target (submerged platform) in the water maze in comparison to the DM, Pre Caf, and Ch Caf groups. Their performance was not significantly different from the control animals. Rotarod testing showed significant role of acute, but not chronic, caffeine administration in enhancing the motor skills. CONCLUSION: STZ -induced DM resulted into defects in memory tasks which are associated with a reduction in the hippocampal NMDA-receptor component of the fEPSP. Acute, but not chronic administration of caffeine could reverse the deteriorating effect of DM on learning and memory.