Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Dec 2012
The role of the NMDA receptors and l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of duloxetine in the forced swimming test.
Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as antidepressant. However, its mechanisms of action are not fully understood. This study investigated the effect of duloxetine in the mouse forced swimming test (FST) and in the tail suspension test (TST) and the involvement of the NMDA receptors and the l-arginine-NO-cGMP pathway in its effect in the FST. ⋯ Moreover, the administration of duloxetine (10mg/kg) produced a reduction in NOx levels in the hippocampus and cerebral cortex. Altogether the results suggest that the effect of duloxetine in the FST is dependent on either a blockade of NMDA receptors or an inhibition of NO. In addition, our results further reinforce the role of NMDA receptors and l-arginine-NO-cGMP pathway, besides the monoaminergic systems, in the mechanism of action of current prescribed antidepressant agents.
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Pharmacol. Biochem. Behav. · Dec 2012
Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous convulsions in lithium-pilocarpine induced status epilepticus in rat model.
Accumulating evidence has shown that neuroinflammation plays a key role in epileptogenesis. However, the efficacy of anti-inflammatory agents for preventing epilepsy remains controversial. Fingolimod (FTY720), a sphingosine-1-phosphate (S1P) analog, has potent anti-inflammatory effects in multiple sclerosis (MS) patients and animal models. ⋯ During 21-34days post-SE, the incidence, duration, frequency and severity of SCs significantly decreased in FTY720 treated rats compared with saline treated rats. Aberrant MFS was also attenuated by FTY720 administration. These results suggest that FTY720 exerts anti-inflammatory and antiepileptogenic effects in lithium-pilocarpine model of epilepsy and it may provide a new therapeutic approach for prevention of epileptogenesis.