This study investigated the effects of chronic neonatal blockade of N-methyl-D-aspartate (NMDA) receptors on NMDA and muscarinic acetylcholine receptor-mediated neurotransmission in adulthood. Rats neonatally treated chronically with MK-801/saline were tested for 40 min, at the age of 14-16 weeks, for locomotor activity in an open field immediately after acute administration of MK-801 (0.2 mg/kg) or scopolamine (0.4-2.0 mg/kg). Rats neonatally treated with MK-801 showed significantly higher locomotor activity than those treated with saline. Acute MK-801 administration caused hyperlocomotion regardless of neonatal treatment, but the effect was more potent in rats neonatally treated with MK-801. In contrast, acute scopolamine administration did not cause hyperlocomotion in rats neonatally treated with saline, but significantly increased locomotion in those neonatally treated with MK-801. The results suggest that chronic neonatal NMDA receptor blockade causes changes in glutamatergic and cholinergic transmission in adulthood long after the cessation of treatment. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.