بررسي تاثير پيتوليسانت بر پتانسيلهاي ميداني مسير جانبي شافر هيپوكمپ

eva‎luation of the effect of pitolisant on field potentials in the hippocampal Schaffer-collateral pathway

زيست شناسي گياهي و جانوري

The role of the brainʹs histaminergic system in memory has been extensively studied. However, the circuitry and cellular mechanisms of memory regulation by histamine are not fully understood. Pitolisant is a histamine H3 receptor inverse agonist, which has been used for the treatment of narcolepsy and is known to have potential anti-seizure properties. Yet, the potential effects of pitolisant in memory formation or the probable mechanisms have not been investigated. Here, we eva‎luated the effect of intra-cerebral injection of pitolisant on synaptic excitability and long-term potentiation (LTP) induction in the hippocampal Schaffer collateral pathway using a field potential recording system. Adult male Wistar rats were used. Animals were distributed into three groups. Two groups received pitolisant (10 and 100 ng/rat) in the CA1 area of the hippocampus. The corresponding sham group received saline. Paired pulses, input/output (I/O) functions and LTP induction were assessed in the CA1 region of the hippocampus. Paired-pulse fEPSP slope were decreased significantly in the experimental groups receiving pitolisant. Also, I/O fEPSP slope and amplitude were significantly decreased in the experimental groups receiving pitolisant. The fEPSP slope and amplitude after LTP induction decreased in the experimental groups receiving pitolisant in a significant manner. Overall, the results indicate detrimental effects of intra-CA1 injection of pitolisant on the probability of glutamate releases, synaptic excitability and long-term plasticity of the hippocampal CA1 area neurons, which should be kept in mind for the use of this drug as a medication in the control of brain disorders.

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