Abstract
alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs) have been targeted to improve cognition in different neurological and psychiatric disorders. Nevertheless, no alpha 7nAChR activating ligand has been clinically approved. Here, we investigated the effects of antagonizing alpha 7nAChRs using the selective antagonist methyllycaconitine (MLA) on receptor activity in vitro and cognitive functioning in vivo. Picomolar concentrations of MLA significantly potentiated receptor responses in electrophysiological experiments mimicking the in vivo situation. Furthermore, microdialysis studies showed that MLA administration substantially increased hippocampal glutamate efflux which is related to memory processes. Accordingly, pre-tetanus administration of low MLA concentrations produced longer lasting potentiation (long-term potentiation, LTP) in studies examining hippocampal plasticity. Moreover, low doses of MLA improved acquisition, but not consolidation memory processes in rats. While the focus to enhance cognition by modulating alpha 7nAChRs lies on agonists and positive modulators, antagonists at low doses should provide a novel approach to improve cognition in neurological and psychiatric disorders.
Original language | English |
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Article number | 109338 |
Pages (from-to) | 1-8 |
Number of pages | 8 |
Journal | Cellular Signalling |
Volume | 62 |
DOIs | |
Publication status | Published - Oct 2019 |
Keywords
- alpha 7 nicotinic acetylcholine receptors
- Ligand-gated ion channel
- Antagonist
- Receptor activity
- Long-term potentiation
- Memory acquisition
- LONG-TERM POTENTIATION
- ACETYLCHOLINE-RECEPTORS
- BINDING-SITES
- OBJECT RECOGNITION
- IMPROVES MEMORY
- ION CHANNELS
- ONE-TRIAL
- MECHANISMS
- AGONIST
- SYSTEM