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

• Published in: Behavioural brain research 2005-02, Vol.157 (2), p.369-377
• Main Authors: Degen, S.B., Ellenbroek, B.A., Wiegant, V.M., Cools, A.R.
• Format: Article
• Language: English
• Subjects: Age Factors; Analysis of Variance; Animals; Animals, Newborn - growth & development; Apomorphine; Apomorphine - pharmacology; Behavioral psychophysiology; Biological and medical sciences; Biomarkers; Development; Disease Models, Animal; Dopamine Agonists - pharmacology; Early postnatal manipulation; Female; Fundamental and applied biological sciences. Psychology; Genotype; Handling; Handling (Psychology); Male; Miscellaneous; Phenotype; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Inbred Strains; Schizophrenia; Schizophrenia - physiopathology; Selection line; Species Specificity; Stereotyped Behavior - drug effects; Stress, Psychological - physiopathology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2004.08.002

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.