The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats

Frontiers in Neuroscience
Nermin EissaBassem Sadek

Abstract

The role of Histamine H3 receptors (H3Rs) in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP) and novel object recognition (NOR) task in adult male rats, using donepezil (DOZ) as a standard drug. Acute systemic pretreatment with DL77 (2.5, 5, and 10 mg/kg, i.p.) significantly ameliorated memory deficits induced with MK801 in PAP (allP< 0.05,n= 7). The ameliorative effect of most promising dose of DL77 (5 mg/kg, i.p.) was reversed when rats were co-injected with the H3R agonistR-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.) (p= 0.701 for MK801-amnesic group vs. MK801+DL77+RAMH group,n= 6). In the NOR paradigm, DL77 (5 mg/kg, i.p.) counteracted long-term memory (LTM) deficits induced with MK801 (P< 0.05,n= 6-8), and the DL77-provided effect was similar to that of DOZ (p= 0.788,n= 6-8), and was reversed when rats were co-injected with RAMH (10 mg/kg, i.p.) (p= 0.877,n= 6, as compared to the (MK801)-amnesic group). However, DL77 (5 mg/kg, i.p.) did not alter sh...Continue Reading

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Citations

Aug 22, 2018·British Journal of Pharmacology·Gustavo ProvensiMaria Beatrice Passani
Jun 6, 2018·Frontiers in Neuroscience·Nermin EissaBassem Sadek
Sep 29, 2020·Frontiers in Neuroinformatics·Dandan LiBin Wang
Sep 4, 2020·European Journal of Medicinal Chemistry·Dorota ŁażewskaKatarzyna Kieć-Kononowicz

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