Antidepressant-like effect of 7-nitroindazole in the forced swimming test in rats.
BACKGROUND
There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models.


OBJECTIVE
In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined.


METHODS
The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents.


RESULTS
7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time.


CONCLUSIONS
Our findings suggest that NO might be an important modulator of depression in rats.
Yildiz
F
F
Kocaeli University, Faculty of Medicine, Department of Pharmacology, Turkey. ferden@ato.org.tr
Erden
B F
BF
Ulak
G
G
Utkan
T
T
Gacar
N
N
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007103:Immobilization; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D007191:Indazoles; D001120:Arginine; C080122:7-nitroindazole