The development of various somatic markers is retarded in an animal model for schizophrenia, namely apomorphine-susceptible rats

Although schizophrenia usually sets on after puberty, deviations of normal development exist in pre-schizophrenic children. To investigate the presence of early developmental abnormalities in a valid animal model for schizophrenia, we delineated line-specific developmental differences between apomorphine-susceptible rats (APO-SUS), which share many features with schizophrenic patients, and their counterpart, apomorphine-unsusceptible rats (APO-UNSUS). A battery of somatic developmental markers was assessed in naïve animals on postnatal day (PND) 4 and in animals from PND 0 to PND 60. Three comparisons were made: naïve APO-SUS and naïve APO-UNSUS rats on PND 4; naïve and handled APO-SUS and APO-UNSUS rats on PND 4; handled APO-SUS rats and handled APO-UNSUS rats across the initial 60 PND's. Naïve APO-SUS rats developed much slower than naïve APO-UNSUS rats as far as it concerns digit-separation, anogenital-distance, rooting-reflex, and body-displacement on PND 4, thereby underlining the validity of the APO-SUS rats as model for aspects of schizophrenia. Handling on PND 0-3 retarded the development of both types of rat, implying that early life events have long-lasting effects on pure-somatic markers. Finally, handling from PND 0 to PND 60 had a more pronounced retardation effect in APO-UNSUS rats than in APO-SUS rats. It is suggested that the APO-SUS rats are not affected as much as the APO-UNSUS rats, because they are already overwhelmed by other subliminal stimuli that have no effect on APO-UNSUS rats. In conclusion: (1) the APO-SUS rat, which is a valid model for schizophrenia, has a retarded development just as pre-schizophrenic children have; (2) early postnatal manipulations have immediate and long-lasting effects on the rodents' morphology; and (3) subchronic, early postnatal handling has a greater effect in APO-UNSUS rats than in APO-SUS rats. The impact of these data for APO-SUS rats as a model for schizophrenia is discussed.