Effects of schizophrenomimetics on the expression of the CCN1 (CYR 61) gene encoding a matricellular protein in the infant and adult neocortex of the mouse and rat.

The acute systemic administration of a schizophrenomimetic phencyclidine [5 or 10 mg/kg, subcutaneously (s.c.)] markedly up-regulated the neocortical expression of the CCN1 gene encoding a secreted extracellular matrix-associated protein at postnatal day 56, but not at postnatal day 8, after 60 min in the mouse and rat. The development-dependent nature of the up-regulation between postnatal days 8 and 56 seems to be similar to that of the adult type phencyclidine-induced abnormal behaviours, which have been considered to be models of schizophrenic symptoms. In the young adult rat, 5, 10, and 20 mg/kg phencyclidine (given s.c.) induced an increase in the CCN1 gene transcripts in a dose-related and bell-shaped manner with a maximum at the dose of 10 mg/kg, 60 min post-injection. Other schizophrenomimetics, dizocilpine (1 mg/kg) and methamphetamine (4.8 mg/kg), also caused a prominent up-regulation of the neocortical expression of the CCN1 gene in adult rats. These results indicate that the CCN1 gene or protein could be implicated in a molecular cascade associated with the age-dependent onset of schizophrenia that usually occurs after puberty.