Increased DOI-induced head shakings in adult rats neonatally treated with MK-801

We examined the effects of neonatal treatment with MK-801 on 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shaking as well as [(3)H]ketanserin binding in adult rats. Neonatal rats were injected with MK-801 (0.25 mg/kg, s.c., twice daily) or with saline from postnatal days (PND) 7-18. At PND 60, a statistically significant increase in the frequency of head shaking induced by DOI (1.0 mg/kg, s.c.) was observed in the rats neonatally treated with MK-801, compared to saline-treated rats, without any change in the specific [(3)H]ketanserin binding in the frontal cortex. These results suggest that repeated NMDA receptor blockades during the critical period of brain development produce a long lasting hyper-responsiveness in the 5-HT(2A) receptor-mediated behavior, interfering with the development of neural circuits related to the behavior.