Antidepressant-like effect of pioglitazone in the forced swimming test in mice: The role of PPAR-gamma receptor and nitric oxide pathway

• Our study demonstrates that oral administration of pioglitazone in mice manifest the antidepressant-like effect in forced swimming test. • This antidepressant-like effect of pioglitazone could not be attributed to an increase in the locomotor activity. • This antidepressant-like effect of pioglita...

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Veröffentlicht in:Behavioural brain research 2011-10, Vol.224 (2), p.336-343
Hauptverfasser: Sadaghiani, Mohammad Salehi, Javadi-Paydar, Mehrak, Gharedaghi, Mohammad Hadi, Fard, Yashar Yousefzadeh, Dehpour, Ahmad Reza
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Sprache:eng
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Zusammenfassung:• Our study demonstrates that oral administration of pioglitazone in mice manifest the antidepressant-like effect in forced swimming test. • This antidepressant-like effect of pioglitazone could not be attributed to an increase in the locomotor activity. • This antidepressant-like effect of pioglitazone is mediated at least in part through PPARγ receptors and nitric oxide pathway. In this study, the potential antidepressant-like effects of pioglitazone and the possible involvement of peroxisome proliferator-activated receptor gamma (PPARγ) and nitric oxide system in antidepressant effects of pioglitazone were determined using forced swimming test (FST) in mice. After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4 min was evaluated. Pioglitazone was administered orally with doses (5, 10, 20 and 30 mg/kg) 2 and 4 h before FST. To assess the involvement of PPARγ in the possible antidepressant effect of pioglitazone, GW9662, a PPARγ antagonist (2 mg/kg) was administered before pioglitazone (20 mg/kg). For determination of possible role of nitric oxide pathway in this effect, a non-specific NOS inhibitor, Nω-nitro- l-arginine methyl ester ( l-NAME, 10 mg/kg, i.p.), a specific iNOS inhibitor, aminoguanidine (50 mg/kg, i.p.), or a NO precursor, l-arginine (750 mg/kg, i.p.) was co-administered with pioglitazone, either 2 or 4 h before FST. The immobility time significantly decreased after pioglitazone administration (20 and 30 mg/kg). GW-9662 significantly reversed antidepressant effect of pioglitazone administered 2 and 4 h prior to FST. Co-administration of non-effective doses of pioglitazone and l-NAME revealed antidepressant-like effect in FST; while, co-administration of non-effective doses of aminoguanidine and pioglitazone did not affect the immobility time. l-Arginine also reversed the antidepressant-like effect of pioglitazone. The antidepressant-like effect of pioglitazone on mice in the FST is mediated at least in part through PPARγ receptors and nitric oxide pathway.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2011.06.011