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Co-administration of the low dose of orexin and nitrergic antagonists induces an antidepressant-like effect in mice

Alijanpour, S. and Khakpai, F. and Ebrahimi-Ghiri, M. and Zarrindast, M.-R. (2019) Co-administration of the low dose of orexin and nitrergic antagonists induces an antidepressant-like effect in mice. Biomedicine and Pharmacotherapy, 109. pp. 589-594.

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It is now well-established that orexins (OXs) and their receptors are involved in the pathophysiology of depression. Considering the evidence indicating the importance of nitric oxide (NO) system in the mood modulation, this study investigated the effect of intraperitoneal (i.p.) administration of orexin 1 (OX1) receptor antagonist -SB334867- alone or in combination with NO agents on depression using the forced swimming test (FST), tail suspension test (TST) and the number of crossings in open-field test (OFT) in mice. Our results indicated that administration of SB334867 at the dose of 0.5 mg/kg decreased the immobility time in the FST without effect on locomotor activity, suggesting an antidepressant-like effect of SB334867. Moreover, L-Arginine (a NO precursor; 750 mg/kg) or L-NAME (a non-selective nitric oxide synthase (NOS) inhibitor, 10 mg/kg) administration by itself decreased the immobility time in the FST. Interestingly, co-administration of a sub-threshold dose of L-NAME, but not L-Arginine, in combination with an ineffective dose of SB334867 produced an antidepressant-like effect in the FST and TST. It should be noted, none of the drugs elicited significant effects on the locomotor activity in the OFT. Altogether, the present data propose that a combination of the sub-effective dose of OX and NO antagonists can be evaluated as an option for the clinical treatment of depression in humans. © 2018 Elsevier Masson SAS

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: 1 (2 methyl 6 benzoxazolyl) 3 (1,5 naphthyridin 4 yl)urea; antidepressant agent; arginine; n(g) nitroarginine methyl ester; orexin 1 receptor; 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; antidepressant agent; benzoxazole derivative; n(g) nitroarginine methyl ester; nitric oxide; orexin; urea, animal experiment; animal model; antidepressant activity; Article; controlled study; depression; forced swim test; immobility time; locomotion; low drug dose; male; mouse; nonhuman; number of crossings; open field test; priority journal; tail suspension test; analogs and derivatives; animal; antagonists and inhibitors; combination drug therapy; depression; dose response; drug effect; immobilization; metabolism; physiology; psychology; swimming; treatment outcome, Animals; Antidepressive Agents; Benzoxazoles; Depression; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hindlimb Suspension; Locomotion; Male; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide; Orexins; Swimming; Treatment Outcome; Urea
Subjects: QTفیزیولوژی
فارماکولوژی QV
> دانشکده داروسازی > فارماکولوژی QV

مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 26 Jun 2019 06:55
Last Modified: 26 Jun 2019 06:55
URI: http://eprints.goums.ac.ir/id/eprint/9956

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