title: Antidepressant-like effect of pioglitazone in the forced swimming test in mice: the role of PPAR-gamma receptor and nitric oxide pathway.
abstract: 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.
  
  
  METHODS
  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 4h before FST. To assess the involvement of PPARγ in the possible antidepressant effect of pioglitazone, GW9662, a PPARγ antagonist (2mg/kg) was administered before pioglitazone (20mg/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, 10mg/kg, i.p.), a specific iNOS inhibitor, aminoguanidine (50mg/kg, i.p.), or a NO precursor, L-arginine (750 mg/kg, i.p.) was co-administered with pioglitazone, either 2 or 4h before FST.
  
  
  RESULTS
  The immobility time significantly decreased after pioglitazone administration (20 and 30 mg/kg). GW-9662 significantly reversed antidepressant effect of pioglitazone administered 2 and 4h 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.
  
  
  CONCLUSIONS
  The antidepressant-like effect of pioglitazone on mice in the FST is mediated at least in part through PPARγ receptors and nitric oxide pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Salehi
authors.initials: MS
authors.lastname: Sadaghiani
authors.forename: Mehrak
authors.initials: M
authors.lastname: Javadi-Paydar
authors.forename: Mohammad Hadi
authors.initials: MH
authors.lastname: Gharedaghi
authors.forename: Yashar Yousefzadeh
authors.initials: YY
authors.lastname: Fard
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077205:Pioglitazone; D013550:Swimming / Q000523:psychology*; D045162:Thiazolidinediones / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone