Abstracts

Rationale: Rationale: Brain pro-inflammatory markers are known to be increased in the central nervous system by both, epilepsy and depression. Recently we found that antiepileptic drugs that inhibit cerebral sodium channels and glutamate release from hippocampal isolated nerve endings, decrease brain inflammatory markers ex-vivo and overcome the rise in brain inflammation induced by seizures (Gomez et al. 2014 J. Neurochem. 130: 770-779). In previous studies we reported that cerebral presynaptic sodium channel permeability and glutamate release were decreased by the antidepressant sertraline (Aldana and Sitges 2012 J. Neurochem. 121: 197-205), and that sertraline was an effective inhibitor of tonic-clonic seizures in the rat (Sitges et al. 2012, Epilepsy & Behavior 25: 511-516). Therefore, in the present study, the possible changes in the expression of the pro-inflammatory markers, IL-1β and TNF-α, in the hippocampus of rats pre-administered with sertraline were investigated, as well as the capability of sertraline to overcome the increase in the cerebral inflammatory markers induced by seizures. Methods: Methods: The effect on the expression of IL-1β and TNF-α mRNA in the hippocampus of rats pre-administered once or for seven consecutive days with a low dose (0.75 mg/kg) of sertraline was determined by RT-PCR. The effect of sertraline (at doses in the range from 0.75 to 25 mg/kg) on the rise in IL-1β and TNF-α mRNA expression accompanying generalized tonic-clonic seizures induced by the convulsive agents, 4-aminopyridine (4-AP) or pentylenetetrazole (PTZ), and on the increase in IL-1β and TNF-α mRNA expression induced by lipopolysaccharide (LPS) also was investigated. Results: Results: Under basal conditions, A single 0.75 mg/kg sertraline dose was able to reduce IL-1βmRNA expression in the hippocampus, and TNF-α mRNA expression was also reduced after the repeated doses. Tonic-clonic seizures induced by 4-AP and the increase in the expression of IL-1β and TNF-α accompanying seizures were insensitive to the single 0.75 mg/kg sertraline dose, but were completely abolished by the administration of 0.75 mg/kg sertraline for one week. The increase in IL-1β and TNF-αmRNA expression accompanying seizures induced by PTZ were also sertraline sensitive; as was the increase in pro-inflammatory cytokines expression induced by the inoculation of 100 mg/kg LPS. Conclusions: Conclusion: 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.