ArticleIranian journal of basic medical sciences2026
Pitolisant disrupts memory consolidation and hippocampal synaptic plasticity: Impaired excitability and long-term potentiation in the CA1 area.
Article in Iranian journal of basic medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: The histaminergic system plays a vital role in memory function, but the underlying cellular and circuit mechanisms remain poorly understood. Pitolisant, an inverse agonist of the histamine H3 receptor (H3R), is widely used in the treatment of narcolepsy and has shown potential anti-seizure effects. However, its impact on memory and synaptic plasticity is unclear. This study investigated the effects of intracerebroventricular administration of pitolisant on passive avoidance memory consolidation. Meanwhile, the impact of pitolisant on synaptic excitability, short-term plasticity, and long-term potentiation (LTP) in the hippocampus was investigated. Materials and Methods: Adult male Wistar rats received pitolisant (10 or 100 µg/rat; ICV) or saline immediately after training in the passive avoidance apparatus to test memory consolidation. Meanwhile, pitolisant was microinjected into the CA Results: Pitolisant significantly impaired memory consolidation. It also reduced the fEPSP slope in I/O function and paired-pulse facilitation, suggesting impaired synaptic excitability and increased presynaptic inhibition. Additionally, LTP was reduced in pitolisant-treated groups, indicating disrupted long-term plasticity. Conclusion: These findings highlight a potential inhibitory effect of pitolisant on passive-avoidance memory consolidation in healthy rats and on hippocampal synaptic function, raising concerns about its use in neurological disorders.
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