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Kappa Opioid Receptor Agonist Administration in Olfactory Bulbectomized Mice Restores Cognitive Impairment through Cholinergic Neuron Activation.

Biol. Pharm. Bull.2018;41(6):957-960. doi:10.1248/bpb.b18-00115
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摘要


Olfactory bulbectomized (OBX) mice are characterized by impaired performance in the passive avoidance test and decreased number of cholinergic neurons in the hippocampus. Several studies have reported that κ-opioid receptor agonists improve cognitive function in mice. However, their influence on OBX-induced cognitive dysfunction remains unclear. To address this question, we evaluated the effects of the endogenous κ-opioid receptor agonist dynorphin A (Dyn A) and the selective agonist trans-(-)-U-50488 on the behavior of OBX mice in the passive avoidance test. The cognitive dysfunction of OBX mice was significantly recovered by the intracerebroventricular administration of Dyn A or trans-(-)-U-50488. The effects of these two agonists were counteracted by the selective κ-opioid receptor antagonist nor-binaltorphimine or the inhibitor of acetylcholine release β-bungarotoxin. These findings suggest that κ-opioid receptor agonists produce anti-dementia effects through activation of cholinergic neurons in OBX mice.

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