Endomorphin-1 attenuates Aβ42 induced impairment of novel object and object location recognition tasks in mice

• Published in: Brain research 2015-12, Vol.1629, p.210-220
• Main Authors: Zhang, Rui-san, Xu, Hong-jiao, Jiang, Jin-hong, Han, Ren-wen, Chang, Min, Peng, Ya-li, Wang, Yuan, Wang, Rui
• Format: Article
• Language: English
• Subjects: Alzheimer׳s disease; Amyloid beta-Peptides - administration & dosage; Amyloid beta-Peptides - toxicity; Amyloid-β; Analgesics, Opioid - administration & dosage; Animals; Endomorphin-1; Infusions, Intraventricular; Male; Memory Disorders - chemically induced; Memory Disorders - prevention & control; Mice; Naloxone - administration & dosage; Narcotic Antagonists - administration & dosage; Neurology; Oligopeptides - administration & dosage; Peptide Fragments - administration & dosage; Peptide Fragments - toxicity; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - antagonists & inhibitors; Receptors, Opioid, mu - physiology; Recognition (Psychology) - drug effects; Recognition (Psychology) - physiology; Recognition memory
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2015.10.028

Abstract A growing body of evidence suggests that the agglomeration of amyloid-β (Aβ) may be a trigger for Alzheimer׳s disease (AD). Central infusion of Aβ42 can lead to memory impairment in mice. Inhibiting the aggregation of Aβ has been considered a therapeutic strategy for AD. Endomorphin-1 (EM-1), an endogenous agonist of μ-opioid receptors, has been shown to inhibit the aggregation of Aβ in vitro. In the present study, we investigated whether EM-1 could alleviate the memory-impairing effects of Aβ42 in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. We showed that co-administration of EM-1 was able to ameliorate Aβ42 -induced amnesia in the lateral ventricle and the hippocampus, and these effects could not be inhibited by naloxone, an antagonist of μ-opioid receptors. Infusion of EM-1 or naloxone separately into the lateral ventricle had no influence on memory in the tasks. These results suggested that EM-1 might be effective as a drug for AD preventative treatment by inhibiting Aβ aggregation directly as a molecular modifier.