Abstracts

Rationale: Post-status epilepticus (SE) chronic epilepsy in rats has been validated as a model of comorbidity between epilepsy and depression by behavioral, biochemical and neuroendocrine assays. Activation of an inflammatory cytokine interleukin-1? in the hippocampus has been suggested as a mechanism of epilepsy-associated depression (Mazarati et al., Neurobiol. Dis. 2010; 37:461-467). Another hallmark of neuroinflammation - microglia activation - has been implicated both in post-SE epilepsy and in major depression. We studied whether a microglia inhibitor minocycline (MINO) would exhibit antidepressant and anticonvulsant effects in post-SE rats. Methods: Two months after LiCl-pilocarpine SE, adult Wistar rats were examined for the presence of symptoms of depression: dysregulation of hypothalamo-pituitary-adrenocortical (HPA) axis using dexamethasone (DEX)-corticotropin releasing hormone (CRH) test coupled with plasma corticosterone (CORT) radioimmunoassay; despair using forced swim test (FST); anhedonia using taste preference saccharin consumption test. MINO (50 mg/kg/day) was administered for 10 days. Animals were monitored for spontaneous seizures for 10 days prior to, and throughout MINO treatment. At the end of MINO regimen, tests for depression were repeated. Results: Post-SE rats exhibited depression-like impairments. Dysregulation of HPA axis was evident as the decrease of CORT level (81% of that in controls); failure of DEX to suppress CORT (post-DEX/pre-DEX CORT levels were 78% post-SE and 34% in controls); exacerbated response to CRH (post-CRH/pre-CRH CORT levels were 620% post-SE and 315% in controls). Despair was evident as the increased immobility time in the FST (59% of total swimming time post-SE vs. 27% in controls, p<0.05). Anhedonia was revealed by the absence of preferential consumption of saccharin solution versus tap water (saccharin/saccharin water consumption was 48% post-SE and 78% in controls). Treatment with MINO reversed anhedonia (saccharin consumption was 73% of total fluid, p<0.05 vs. before MINO, p>