Abstract
We recently discovered that the antidepressant sertraline is an effective inhibitor of hippocampus presynaptic Na+ channel permeability in vitro and of tonic-clonic seizures in animals in vivo. Several studies indicate that the pro-inflammatory cytokines in the central nervous system are increased in epilepsy and depression. On the other hand inhibition of Na+ channels has been shown to decrease pro-inflammatory cytokines in microglia. Therefore, the possibility that sertraline could overcome the rise in pro-inflammatory cytokine expression induced by seizures has been investigated. For this purpose, IL-1β and TNF-α mRNA expression was determined by RT-PCR in the hippocampus of rats administered once, or for seven consecutive days with sertraline at a low dose (0.75 mg/kg). The effect of sertraline at doses within the range of 0.75 to 25 mg/kg on the increase in IL-1β and TNF-α mRNA expression accompanying generalized tonic-clonic seizures, and increase in the pro-inflammatory cytokines expression induced by lipopolysaccharide was also investigated. We found that under basal conditions, a single 0.75 mg/kg sertraline dose decreased IL-1β mRNA expression, and also TNF-α expression after repeated doses. The increase in IL-1β and TNF-α expression induced by the convulsive agents and by the inoculation of lipopolysaccharide in the hippocampus was markedly reduced by sertraline also. Present results indicate that a reduction of brain inflammatory processes may contribute to the anti-seizure sertraline action, and that sertraline can be safely and successfully used at low doses to treat depression in epileptic patients.
Highlights
Psychiatric disorders, and depression, are known as frequent co-morbidities in patients with epilepsy [1,2,3,4,5,6,7]
Group 5 (G5), was administered once with saline followed by 4AP; Group 6 (G6), was administered once with 0.75 mg/kg sertraline followed by 4-AP, Group 7 (G7) with 0.75 mg/kg sertraline daily for one week, followed by 4-AP, Group 8 (G8) with saline followed by PTZ; Group 9 (G9) with sertraline at a dose of 2.5 mg/kg followed by PTZ, and Group 10 (G10) with 25 mg/kg sertraline followed by PTZ
We show that in the control groups injected with the vehicle once (G1), or 7 times (G3), the baseline mRNA expression of both cytokines is very similar
Summary
Psychiatric disorders, and depression, are known as frequent co-morbidities in patients with epilepsy [1,2,3,4,5,6,7]. Voltage sensitive Na+ channels are involved in exacerbating neuronal excitability during seizures. Among the most effective of all anti-epileptic drugs are those capable of decreasing voltage sensitive Na+ channel permeability. In hippocampal isolated nerve endings, sertraline, a drug broadly prescribed for the treatment of depression [21], in addition to its action on the 5-HT transporter, resulted in a potent and effective inhibitor of voltage sensitive Na+ channel permeability [22]. In mixed glial cell cultures the Na+ channel blocker, tetrodotoxin, as well as the classic anti-epileptic drug, phenytoin, whose mechanism of action involves inhibition of Na+ channels, reduced the secretion of the pro-inflammatory cytokines interleukin-1beta (IL-1b) and TNF-a induced by lipopolysaccharide [24]. We measured the effect of sertraline on the increase in those pro-inflammatory cytokines induced by seizures
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
