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Anticonvulsant Effect of Minocycline on Pentylenetetrazole-Induced Seizure in Mice: Involvement of Nitric Oxide and N-Methyl-D-Aspartate Receptor Publisher Pubmed



Aminikhoei H1, 2 ; Kordjazy N3, 4 ; Hajmirzaian A3, 4 ; Amiri S3, 5 ; Hajmirzaian A3, 4 ; Shirzadian A3 ; Hasanvand A7 ; Balalidehkordi S8 ; Hassanipour M9, 10 ; Dehpour AR3, 4
Authors
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Authors Affiliations
  1. 1. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
  2. 2. Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3T 2N2, MB, Canada
  6. 6. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, United States
  7. 7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
  8. 8. Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  9. 9. Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  10. 10. Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Source: Canadian Journal of Physiology and Pharmacology Published:2018


Abstract

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-D-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor NG-L-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDA receptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors. © 2018, Canadian Science Publishing. All rights reserved.
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