Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Eissa, Nermin, Khan, Nadia, Ojha, Shreesh K., Łazewska, Dorota, Kieć-Kononowicz, Katarzyna, Sadek, Bassem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816071/
https://www.ncbi.nlm.nih.gov/pubmed/29483860
http://dx.doi.org/10.3389/fnins.2018.00042
_version_ 1783300610694578176
author Eissa, Nermin
Khan, Nadia
Ojha, Shreesh K.
Łazewska, Dorota
Kieć-Kononowicz, Katarzyna
Sadek, Bassem
author_facet Eissa, Nermin
Khan, Nadia
Ojha, Shreesh K.
Łazewska, Dorota
Kieć-Kononowicz, Katarzyna
Sadek, Bassem
author_sort Eissa, Nermin
collection PubMed
description 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 (all P < 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 agonist R-(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 short-term memory (STM) impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801)-amnesic group). Moreover, DL77 (5 mg/kg) failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM) (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6), demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating neurotransmitters related to neurodegenerative disorders, e.g., AD.
format Online
Article
Text
id pubmed-5816071
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-58160712018-02-26 The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats Eissa, Nermin Khan, Nadia Ojha, Shreesh K. Łazewska, Dorota Kieć-Kononowicz, Katarzyna Sadek, Bassem Front Neurosci Neuroscience 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 (all P < 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 agonist R-(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 short-term memory (STM) impairment in NOR test (p = 0.772, n = 6–8, as compared to (MK801)-amnesic group). Moreover, DL77 (5 mg/kg) failed to modify anxiety and locomotor behaviors of animals innate to elevated-plus maze (EPM) (p = 0.67 for percentage of time spent exploring the open arms, p = 0.52 for number of entries into the open arms, p = 0.76 for percentage of entries into the open arms, and p = 0.73 number of closed arm entries as compared to saline-treated groups, all n = 6), demonstrating that the procognitive effects observed in PAP or NOR tests were unconnected to alterations in emotions or in natural locomotion of tested animals. These results signify the potential involvement of H3Rs in modulating neurotransmitters related to neurodegenerative disorders, e.g., AD. Frontiers Media S.A. 2018-02-12 /pmc/articles/PMC5816071/ /pubmed/29483860 http://dx.doi.org/10.3389/fnins.2018.00042 Text en Copyright © 2018 Eissa, Khan, Ojha, Łazewska, Kieć-Kononowicz and Sadek. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Eissa, Nermin
Khan, Nadia
Ojha, Shreesh K.
Łazewska, Dorota
Kieć-Kononowicz, Katarzyna
Sadek, Bassem
The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title_full The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title_fullStr The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title_full_unstemmed The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title_short The Histamine H3 Receptor Antagonist DL77 Ameliorates MK801-Induced Memory Deficits in Rats
title_sort histamine h3 receptor antagonist dl77 ameliorates mk801-induced memory deficits in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816071/
https://www.ncbi.nlm.nih.gov/pubmed/29483860
http://dx.doi.org/10.3389/fnins.2018.00042
work_keys_str_mv AT eissanermin thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT khannadia thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT ojhashreeshk thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT łazewskadorota thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT kieckononowiczkatarzyna thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT sadekbassem thehistamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT eissanermin histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT khannadia histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT ojhashreeshk histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT łazewskadorota histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT kieckononowiczkatarzyna histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats
AT sadekbassem histamineh3receptorantagonistdl77amelioratesmk801inducedmemorydeficitsinrats