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

• Published in: Biological & pharmaceutical bulletin Vol. 41; no. 6; pp. 957 - 960
• Main Authors: Takahashi, Kohei, Nakagawasai, Osamu, Sugawara, Masae, Sato, Atsushi, Nemoto, Wataru, Tadano, Takeshi, Tan-No, Koichi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.06.2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acetylcholine; Activation; Avoidance; Bungarotoxin; Cholinergic nerves; cholinergic neuron; Cognitive ability; Dementia disorders; Dynorphin; Dynorphin A; Intracerebroventricular administration; memory; Mice; Narcotics; Neurons; olfactory bulbectomy; Opioid receptors (type kappa); κ-opioid; olfactory bulbectomy; cholinergic neuron; κ-opioid; memory
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00115

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.