Journal de recherche et de thérapie en toxicomanie

Abstrait

An Attempt of Non-human Primate Modeling of Schizophrenia with Neonatal Challenges of Epidermal Growth Factor

Miwako Sakai, Masafumi Kashiwahara, Akiyoshi Kakita and Hiroyuki Nawa

Inflammatory cytokines are implicated in the neurodevelopmental hypothesis for schizophrenia. Based on this hypothesis, we studied the establsihment of rodent models for schizophrenia by subcutaneously challenging rat or mouse neonates with various cytokines. Because of the physical and behavioral difference between animal species; however, it is difficult to fully evaluate the appropriateness of rodent models. To overcome this problem, we attempted to establish a non-human primate model of schizophrenia. We subcutaneously injected epidermal growth factor (EGF: 0.3 mg/kg/day) to 3 male neonatal cynomolgus monkeys for a total of 7 or 9 days from 14 days of age. During the following 4 or 5 years, no abnormal behaviors were observed in these monkeys treated with EGF; however, at the age of 6 years, 1 monkey exhibited abnormal behavioral traits: stereotypic movement, vocalization, alert motion, and self injury. It was noteworthy that the monkey often showed agitation and clapped its hands over its eyes and bit his hands in periods of illumination, although not under darkened conditions. The behavioral abnormalities except vocalization were ameliorated by 10-day oral treatment with risperidone at 0.10 mg/kg/day. Although this study needs to be replicated, this case report suggests the possibility that hyper EGF signals at the perinatal stage of non-human primates result in post-pubertal behavioral/cognitive deficits, which possibly imitate some pathological features of human schizophrenia.