title: Fish oil prevents rodent anxious states comorbid with diabetes: A putative involvement of nitric oxide modulation.
abstract: There is an urgent need to understand the pathophysiological mechanisms related to anxiety associated with diabetes, seeking more effective alternative treatments to treat it. For that, the effect of a preventive and prolonged treatment with fish oil (FO), a source of omega-3 polyunsaturated fatty acid, was tested in streptozotocin-diabetic (DBT) rats submitted to the anxiety tests. Additionally, an immunohistochemistry for neuronal NO synthase (nNOS) was performed in brain areas related to anxiety, such as lateral amygdala (AMY), hippocampus (HIP) and dorsolateral periaqueductal gray (dlPAG). Lastly, the effect of NO precursor L-arginine (L-Arg) or nNOS inhibitor 7-nitroindazole (7-NI) was tested in DBT animals treated with vehicle (VEH) or FO. Our data demonstrated that vehicle-treated DBT animals exhibited a more pronounced anxiogenic-like response and also presented high nNOS levels in the AMY, HIP and rostral dlPAG, what were both significantly prevented by FO treatment. This treatment was able to prevent the impairment in locomotor activity besides improving the high glycemic levels in DBT rats. Interestingly, while injection of 7-NI or L-Arg in VEH-treated DBT animals induced an anxiogenic-like and anxiolytic-like effect, respectively; the previous treatment with both L-Arg and 7-NI in FO-DBT animals abolished the anxiolytic-like effect induced by FO treatment. Altogether, our data support the hypothesis that a dysregulation in the NO production in brain areas as AMY, HIP and dlPAG may contribute to the mechanisms that link anxiety and diabetes, and the prevention of nNOS brain expression changes induced by a prolonged treatment with FO may be an important mechanism related to its anxiolytic-like effect.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Isadora Pozzetti
authors.initials: IP
authors.lastname: Siba
authors.affiliation: Faculty of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Stomatology, University of São Paulo, Café Avenue, s/n, 14040-904 Ribeirao Preto, SP, Brazil.
authors.forename: Mariza
authors.initials: M
authors.lastname: Bortolanza
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Maria Aparecida Barbato
authors.initials: MAB
authors.lastname: Frazão Vital
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Joice Maria
authors.initials: JM
authors.lastname: da Cunha
authors.affiliation: Faculty of Odontology of Ribeirão Preto, Department of Morphology, Physiology and Stomatology, University of São Paulo, Café Avenue, s/n, 14040-904 Ribeirao Preto, SP, Brazil.
authors.forename: Elaine Aparecida
authors.initials: EA
authors.lastname: Del Bel
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Coronel H dos Santos Street, s/n, P.O. Box 19031, Curitiba, PR 81540-990, Brazil. Electronic address: janaina.zanoveli@ufpr.br.
authors.forename: Janaína Menezes
authors.initials: JM
authors.lastname: Zanoveli
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000517:prevention & control*; D001120:Arginine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005395:Fish Oils; D007191:Indazoles; D009569:Nitric Oxide; D013311:Streptozocin; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole
keywords: Anxiety; Elevated plus maze; Fish oil; Neuronal nitric oxide synthase; Omega-3 polyunsaturated fatty acids; Streptozotocin