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Antinociceptive and Antidepressive Efficacies of the Combined Ineffective Doses of S-Ketamine and Urb597 Publisher Pubmed



Ebrahimighiri M1 ; Shahini F2 ; Khakpai F3 ; Zarrindast MR2, 4, 5, 6
Authors
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Authors Affiliations
  1. 1. Department of Biology, Faculty of Sciences, University of Zanjan, Zanjan, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  4. 4. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  6. 6. Department of Neuroendocrinology, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Naunyn-Schmiedeberg's Archives of Pharmacology Published:2019


Abstract

Clinical studies have demonstrated that the NMDA receptor antagonist ketamine produces rapid antidepressant responses. There are safety concerns and adverse effects that limit the utilization of ketamine in psychiatry. Some studies have suggested combination therapy for optimal ketamine use. In this study, we evaluated the potential for combination therapy of ineffective doses of ketamine and fatty acid amide hydrolase inhibitor URB597 for the treatment of depression and pain in male NMRI mice. Intraperitoneal administration of ketamine (10 mg/kg) at the time intervals of 115, 145, and 160 min and ketamine (5 mg/kg) at the time interval of 160 min after administration increased the tail-flick latency, indicating an antinociceptive effect. The same doses of ketamine decreased immobility time in the forced swim test (FST), showing an antidepressant-like effect. Moreover, URB597 at the doses of 0.5 and 1 mg/kg induced an antinociceptive effect, while it at the dose of 1 mg/kg produced an antidepressant-like response. Furthermore, co-administration of the ineffective doses of ketamine (2.5 mg/kg) and URB597 (0.1 mg/kg) caused antinociceptive and antidepressant-like effects, while each one of them alone did not alter the performance of mice in the FST and tail-flick tests. It should be noted that none of the treatments alter animal locomotor activity compared to the control group. Therefore, the combined administration of ineffective doses of ketamine and URB597 might be an effective strategy in the therapy of depression and pain. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
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