Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.

Abstract

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABAA receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABAA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABAA receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABAA receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation.

• Authors: Mohammad Nasehi, Parastoo Morteza-Zadeh, Fatemeh Khakpai, Mohammad-Reza Zarrindast
• Journal: Neuroscience (Neuroscience) Vol. 339 Pg. 287-295 (Dec 17 2016) ISSN: 1873-7544 [Electronic] United States
• PMID: 27725215 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• Nootropic Agents
• Receptors, GABA-A
• Muscimol
• Harmine
• harman

Topics

• Animals
• Avoidance Learning (drug effects, physiology)
• CA1 Region, Hippocampal (metabolism, pathology)
• Dose-Response Relationship, Drug
• GABA-A Receptor Agonists (pharmacology)
• GABA-A Receptor Antagonists (pharmacology)
• Harmine (analogs & derivatives, pharmacology)
• Male
• Memory Consolidation (drug effects, physiology)
• Memory Disorders (drug therapy, metabolism, pathology)
• Mice
• Motor Activity (drug effects, physiology)
• Muscimol (pharmacology)
• Nootropic Agents (pharmacology)
• Receptors, GABA-A (metabolism)