Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test.
In the present study we evaluated the involvement of l-arginine/nitric oxide (NO)/cGMP pathway in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test (FST). Lithium, at 30 and 100 mg/kg, significantly reduced the immobility times of mice in the FST, whereas at lower doses (0.5, 5 and 10 mg/kg) had no effect on the immobility time. The NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 10 and 30 mg/kg, and the selective neuronal NOS inhibitor N(omega)-propyl-L-arginine (L-NPA), at 5 and 15 mg/kg, had no significant effects on the FST, whereas they significantly decreased the immobility time at 100 and 30 mg/kg, respectively. Combination of non-effective dose of lithium (10 mg/kg) with low doses of L-NAME (30 mg/kg) or L-NPA (15 mg/kg) significantly reduced the immobility times in the FST. Moreover, the guanylyl cyclase inhibitor ODQ at 50 mg/kg significantly decreased the immobility time of mice, whereas it had not significant effects on the FST at 2, 10 and 20 mg/kg. Combination of lithium (10 mg/kg) with 20 mg/kg ODQ significantly decreased the immobility times in the FST. Non-effective doses of L-arginine (750 mg/kg) or sildenafil (5 mg/kg) significantly reversed the antidepressant-like effect of 30 mg/kg lithium in the FST. Neither of the drugs had effect on the locomotor activity. These data indicate the involvement of L-arginine/NO/cGMP pathway in the antidepressant-like effect of lithium in the mouse FST and also might suggest the concurrent administration of NOS inhibitors and lithium as an appropriate strategy for treatment of depression.
Ghasemi
Mehdi
M
Department of Pharmacology, School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran.
Sadeghipour
Hamed
H
Mosleh
Afsaneh
A
Sadeghipour
Hamid Reza
HR
Mani
Ali Reza
AR
Dehpour
Ahmad Reza
AR
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D018020:Lithium Compounds / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D013550:Swimming
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D018020:Lithium Compounds; D009569:Nitric Oxide