title: Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test.
abstract: Based on clinical studies regarding the beneficial effect of gabapentin in depression, we aimed to evaluate the antidepressant-like properties of gabapentin in mice and also the participation of nitric oxide (NO)/cyclic guanosine monophosphate pathway in this effect. The following drugs were used in this study: gabapentin; N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase (NOS) inhibitor; 7-nitroindazole, a specific neuronal NOS inhibitor; aminoguanidine, a specific inducible NOS inhibitor; L-arginine, a NO precursor; and sildenafil, a phosphodiestrase inhibitor. Finally, we studied the behavioral effects through the forced swimming test (FST) and the changes of the hippocampus NO level through nitrite assay. The immobility time was significantly reduced after gabapentin administration. Co-administration of non-effective doses of gabapentin and L-NAME or 7-nitroindazole (7-NI) resulted in antidepressant-like effect in FST, while aminoguanidine did not affect the immobility time of gabapentin-treated mice. Furthermore, the antidepressant-like property of gabapentin was prevented by L-arginine or sildenafil. Also, the hippocampal nitrite level was significantly lower in gabapentin-treated mice relative to saline-injected mice, and co-administration of 7-NI with sub-effective gabapentin caused a significant decrease in hippocampal nitrite levels. Our results indicate that the antidepressant-like effect of gabapentin in the mice FST model is mediated at least in part through nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Kordjazy
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arya
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Ameli
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Golnoosh
authors.initials: G
authors.lastname: Akhlaghipour
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.|Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.
authors.forename: AhmadReza
authors.initials: A
authors.lastname: Dehpour
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013550:Swimming; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: Cyclic guanosine monophosphate (cGMP); Forced swimming test; Gabapentin; Mice; Nitric oxide