Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice |
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| Affiliation: | 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Neurology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA;1. Laboratório Interdisciplinar de Investigação Médica, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;2. University Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;3. Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX, United States;4. Medical School, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Diamantina, MG, Brazil;5. Laboratory of Cellular and Molecular Pathology, Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;1. Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA, USA;2. Experimental Animals Breeding and Research Center, Faculty of Medicine, Uludag University, Bursa 16059, Turkey;3. Department of Pharmacology and Toxicology, King Saud University, Riyadh, Saudi Arabia;4. Center for Drug Discovery, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC 27709-2194, USA;5. Department of Pharmacology and Therapeutics, University of Florida, P.O. Box 100267, Gainesville, FL 32610-0267, USA;6. Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA |
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| Abstract: | Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. |
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