Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy

Abstract

Wistar derived inbred line, the WAG/Rij rats, genetically absence epilepsy prone and their normal counterparts, outbred Wistar rats, were compared in respect to differences in behavior, in acute and chronic antidepressant imipramine treatment and in the immediate early gene c-fos expression in the brain regions induced by forced swimming test procedure. The WAG/Rij rats as compared with Wistar rats were found to exhibit decreased activity in the open field test, increased immobility in the forced swimming test and decreased sucrose intake (anhedonia). Interline differences indicating increased anxiety in the WAG/Rij rats were not revealed in the light–dark choice, social interaction and elevated plus-maze tests. The WAG/Rij rats in contrast to Wistar rats responded only to chronic antidepressant imipramine treatment with a reduction in their enhanced immobility in the forced swimming test. “Behavioral despair” induced by forced swimming led to c-fos expression in frontal cortex, nucleus accumbens and striatum, terminal regions of three dopaminergic brain systems (mesocortical, mesolimbic, nigrostriatal). The c-fos expression in the brain of WAG/Rij rats was substantially higher than that of Wistar rats. Moreover, the strains differed in the distribution of c-fos expression between brain regions. Results suggest that WAG/Rij rats are prone to adopt passive strategies of behavior in stressful situations, and so in this certain aspect this strain might be regarded as new experimental (genetic) model of depressive-like (passive) behavior accompanying absence epilepsy. Further testing this hypothesis is proceeding. This putative model could be used for the investigation of neurobiological basis and mechanisms of such “double pathology” and for the examination of new concepts of its therapy.