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Abstract
The forced swimming test (FST) has been extensively used as a screening model for
new antidepressant agents. It has been shown that drugs which reduce the amount of
nitric oxide (NO) have the same outcome in this model as classic antidepressants.
In addition, previous studies have shown that methylene blue, which acts as a direct
inhibitor of both NOS and soluble guanylate cyclase (sGC), mimics the effect of clinically
effective antidepressants in patients and in the FST. The present study examined the
effects of the specific inhibitor of the NO-sGC pathway, [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one]
(ODQ) and of the neuronal NOS inhibitor 7-nitroindazole (7-NI) in the FST. We found
that ODQ (10 and 20 mg/kg) significantly decreased the immobility time in the FST
compared to the control. Similarly, injections of 7-NI (30 or 60 mg/kg) reduced immobility
time as well as Imipramine (IMI, 30 mg/kg). Interestingly, L-Arginine (250 mg/kg)
administered in combination with ODQ reversed the effect of ODQ but displayed no effect
when administered alone. Locomotion activity was significantly decreased following
administration of IMI (30 mg/kg) and 7-NI (30 and 60 mg/kg) but was unaffected after
administration of ODQ (10 and 20 mg/kg). These findings suggest that the NO-sGC-cGMP
pathway may play an important role in the mediation of the behavioural effect in the
FST without influence on motor activity.
Copyright 2002 Elsevier Science B.V.