α7 nicotinic acetylcholine receptors (α7nAChRs) are ligand-gated ion channels expressed primarily in the brain. These receptors have been implicated in modulating cognitive functions like episodic memory and attention. Hence, α7nAChR agonists/modulators may be attractive drug candidates to improve cognition in Alzheimer’s disease (AD) and schizophrenia. In the current study, the cognition enhancing properties of low dose administration of selective α7nAChR antagonists were investigated in rats as low doses of methyllycaconitine (MLA) have sporadically been reported to improve cognition in animals. Memory acquisition and consolidation processes were assessed separately with the object recognition task (ORT). The compounds used for these studies were MLA and Compound 7i. Interestingly, it was found that low doses of MLA and Compound 7i improved the acquisition, but not the consolidation processes of object recognition memory at a 24 h retention interval. Conversely, higher doses impaired the memory performance at a shorter 1 h retention interval. In addition, the same compounds were studied in a model of neuronal plasticity, long-term potentiation (LTP). It was demonstrated that pre-tetanus low-dose administration of MLA or Compound 7i produced a longer lasting potentiation, whereas post-tetanus administration had no effect. Microdialysis studies showed that MLA administration substantially increased hippocampal glutamate efflux which has been found to be related to object memory processes. In summary, blocking α7nAChRs with low doses of selective antagonists improves specifically the memory acquisition process. While the main focus of the α7nAChR as a target for cognition enhancement lies on agonists and positive modulators, antagonism of these receptors at low doses might also prove to be a valuable tool for cognition enhancement in AD or schizophrenia.

Blocking α7 nicotinic acetylcholine receptors improves specifically memory acquisition

PUZZO, DANIELA;PALMERI, Agostino;
2015-01-01

Abstract

α7 nicotinic acetylcholine receptors (α7nAChRs) are ligand-gated ion channels expressed primarily in the brain. These receptors have been implicated in modulating cognitive functions like episodic memory and attention. Hence, α7nAChR agonists/modulators may be attractive drug candidates to improve cognition in Alzheimer’s disease (AD) and schizophrenia. In the current study, the cognition enhancing properties of low dose administration of selective α7nAChR antagonists were investigated in rats as low doses of methyllycaconitine (MLA) have sporadically been reported to improve cognition in animals. Memory acquisition and consolidation processes were assessed separately with the object recognition task (ORT). The compounds used for these studies were MLA and Compound 7i. Interestingly, it was found that low doses of MLA and Compound 7i improved the acquisition, but not the consolidation processes of object recognition memory at a 24 h retention interval. Conversely, higher doses impaired the memory performance at a shorter 1 h retention interval. In addition, the same compounds were studied in a model of neuronal plasticity, long-term potentiation (LTP). It was demonstrated that pre-tetanus low-dose administration of MLA or Compound 7i produced a longer lasting potentiation, whereas post-tetanus administration had no effect. Microdialysis studies showed that MLA administration substantially increased hippocampal glutamate efflux which has been found to be related to object memory processes. In summary, blocking α7nAChRs with low doses of selective antagonists improves specifically the memory acquisition process. While the main focus of the α7nAChR as a target for cognition enhancement lies on agonists and positive modulators, antagonism of these receptors at low doses might also prove to be a valuable tool for cognition enhancement in AD or schizophrenia.
nicotinic receptors; long-term potentiation; memory
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/73205
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