Factors regulating the influence of melatonin on hippocampal evoked potentials: comparative studies on different...

Factors regulating the influence of melatonin on the hippocampal glutamergic system in mouse hippocampal slices were evaluated. The sensitivity of hippocampal pyramidal neurons to melatonin (Sigma) was highest at 2 h following slice preparation and then declined with time. This pattern of sensitivity to melatonin correlated well with a reduced binding of melatonin to its receptors. The slices obtained from older animals remained sensitive to melatonin through the entire incubation period. Most of the experiments evaluating the influence of melatonin on hippocampal evoked potentials were performed within 2 h following slice preparation. The effect of melatonin was biphasic: an initial depression of the potential was followed by a recovery/amplification phase. The recovery phase was not a result of melatonin decomposition. The effect of melatonin was similar in three different strains of mice tested: CD-1, C57J/B6, and Swiss Webster. While the melatonin from another vendor (Regis) gave similar results, it was effective at much lower concentrations. In slices obtained from CD-1 light-deprived mice, the sensitivity to melatonin was significantly reduced. Thus, it appears that melatonin may control the hippocampal glutamergic system in a complex manner, which may be regulated by the circadian rhythm. This may influence memory formation in the hippocampus.