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Pitolisant impairs synaptic excitability and long-term potentiation in the hippocampal CA1 area
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Adeleh Badiyifard   , Siamak Beheshti , Mansour Azimzadeh |
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Abstract: (320 Views) |
Introduction: The role of the histaminergic system in memory performance has been widely assessed. However, the underlying circuit and cellular mechanisms are not well understood. Pitolisant is the 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 and/or the probable mechanisms have not been investigated. Here, we evaluated the effect of pitolisant on synaptic excitability and long-term potentiation (LTP) induction in the hippocampal Schaffer collateral pathway.
Methods and Materials: 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. A field potential recording system was used. The input/output (I/O) functions and LTP induction were assessed in the hippocampal CA1 area.
Results: Pitolisant-treated groups showed significant decreases in the fEPSP slope and amplitude of their associated I/O curves compared with the sham group. Also, fEPSP slope and amplitude after LTP induction significantly decreased in the experimental groups receiving pitolisant.
Conclusion: Overall, the results indicate detrimental effects of intra-CA1 injection of pitolisant on 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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| Keywords: Pitolisant, Long-term potentiation, Hippocampus, Synaptic plasticity |
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Full-Text [PDF 248 kb]
(57 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2023/11/25 | Accepted: 2023/08/23 | Published: 2023/08/23
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