A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test.
In the present study we evaluated the involvement of nitric oxide (NO) system in the antidepressant-like effects of chronic lithium administration in the mouse forced swimming test (FST). Administration of lithium chloride (300 mg/L in drinking water for 21 days) had no effect on the immobility of mice in the FST, whereas 600 mg/L lithium caused a significant (P<0.001) decrease in the immobility time compared with control animals. Administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, daily for a week, i.p.) had no significant effect on the immobility time of either control or lithium (300 mg/L)-treated mice, whereas acute administration of non-effective dose of L-NAME (30 mg/kg, i.p.) caused a robust decrease (P<0.01) in the immobility time of lithium (300 mg/L)-treated animals in the FST. Moreover, chronic administration of low dose of the NO precursor L-arginine (200 mg/kg, daily for a week, i.p.) prevented (P<0.001) the antidepressant-like effects of lithium treatment (600 mg/L) in the FST. Acute treatment with L-arginine (200 mg/kg, i.p.) increased (P<0.05) the immobility time of lithium (600 mg/L)-treated mice in the FST. Chronic lithium treatment (600 mg/L but not 300 mg/L) caused a significant (P<0.05) decrease in the serum NO(X) levels in mice compared with controls. Our data suggested that the NO system could be involved in the antidepressant-like effect of chronic lithium treatment in the FST.
Ghasemi
Mehdi
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. m82 ghsemi@yahoo.com
Sadeghipour
Hamed
H
Poorheidari
Gholamreza
G
Dehpour
Ahmad Reza
AR
D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000097:blood; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects*; D018021:Lithium Chloride / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D013550:Swimming / Q000502:physiology*
D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D001120:Arginine; D018021:Lithium Chloride; D019331:NG-Nitroarginine Methyl Ester