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 naive animals on postnatal day (PND) 4 and in animals from PND 0 to PND 60. Three comparisons were made: naive APO-SUS and naive APO-UNSUS rats on PND 4; naive 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. Naive APO-SUS rats developed much slower than naive 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.


CONCLUSIONS
(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.
Degen
S B
SB
Department of Psychoneuropharmacology, University of Nijmegen, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands.
Ellenbroek
B A
BA
Wiegant
V M
VM
Cools
A R
AR
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001058:Apomorphine / Q000494:pharmacology*; D015415:Biomarkers; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006234:Handling, Psychological; D008297:Male; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000503:physiopathology*; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology*
D015415:Biomarkers; D018491:Dopamine Agonists; D001058:Apomorphine