The MAM-E17 schizophrenia rat model: Comprehensive behavioral analysis of pre-pubertal, pubertal and adult rats.

The MAM-E17 model is one of the most accepted schizophrenia rat models, which follows the neurodevelopmental theory of the disease. While symptoms of MAM-E17 rats were studied extensively, their examinations were usually restricted to adulthood and in a few cases to prepuberty. It is well known, however, that schizophrenia symptoms often start at puberty or early adulthood. Therefore the purpose of this study was to investigate the behavioral characteristics of MAM-E17 rats in various tests throughout three different age-periods, namely in prepuberty, late puberty and adulthood. In open field test, MAM-E17 rats displayed increased locomotor activity, elevated sniffing frequency and, as tendency, enhanced rearing activity. The elevated activity turned up in late puberty and remained there in adulthood, too. There was also a deficient prepulse inhibition (PPI) of startle response in late puberty and adulthood, but not before puberty. In rotarod task, MAM-treated rats performed better than control rats. The enhanced performance on rotarod was only present in late puberty and adulthood. In elevated plus maze test MAM-treated rats displayed diminished anxiety mostly in prepuberty. Histological analysis revealed reduced volume and cell disarray in the dorsal hippocampus. This is the first comprehensive study about symptoms of MAM-E17 rats manifested in behavioral tests carried out in prepuberty, late puberty and adulthood. Results display the age-dependent appearance of schizophrenia symptoms in the same rats. The present findings provide basic information to accomplish the schizophrenia related animal research, as well as can also confer further data to develop preventive treatment for human patients.