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

Contains fulltext : 64155.pdf (publisher's version ) (Closed access)A 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. WAG/Rij rats were found to exhibit decreased activity in the open field test, increased immobility in the forced swimming test and decreased sucrose intake (anhedonia) compared to Wistar rats. Interline differences indicating increased anxiety in the WAG/Rij line rats were not revealed in the light-dark choice, social interaction and elevated plus-maze tests. These behavioral changes in WAG/Rij rats are indicative of depression-like state without pronounced anxiety component. Thus, WAG/Rij rats fulfill the criterion of face validity to be an animal model of depression. 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, so they fulfill the criterion of predictive validity for an animal model of depression. "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). 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 the WAG/Rij rats are a new experimental (genetic) model of depression: depression accompanying absence epilepsy and non-associated with increased anxiety