Comorbidity between epilepsy and depression: Role of hippocampal interleukin-1β

Depression is a frequent comorbidity of temporal lobe epilepsy (TLE): however, its mechanisms remain poorly understood and effective therapies are lacking. Augmentation of hippocampal interleukin-1 beta (IL-1 beta) signaling may be a mechanistic factor of both TLE and clinical depression. We examined whether pharmacological blockade of hippocampal interleukin-1 receptor exerts antidepressant effects in an animal model of comorbidity between TLE and depression, which developed in Wistar rats following pilocarpine status epilepticus (SE). In post-SE animals, depression-like state was characterized by behavioral equivalents of anhedonia and despair; dysregulation of the hypothalamo-pituitary-adrenocortical axis; compromised raphe-hippocampal serotonergic transmission. Two-week long bilateral intrahippocampal infusion of human recombinant Interleukin-1 receptor antagonist (IL-1ra) improved all of the examined depressive impairments, without modifying spontaneous seizure frequency and without affecting normal parameters in naive rats. These findings implicate hippocampal IL-1 beta in epilepsy-associated depression and provide a rationale for the introduction of IL-1 beta blockers in the treatment of depression in TLE. (C) 2009 Elsevier Inc. All rights reserved.