MK-801-induced and scopolamine-induced hyperactivity in rats neonatally treated chronically with MK-801.

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.