Differential effects of ketamine and MK-801 on the induction of long-term potentiation.

Ketamine and MK-801 are phencyclidine (PCP)-like noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor that produce a use-dependent blockade of the NMDA receptor-coupled channel. Recent studies have suggested that the binding properties of these drugs to the NMDA receptor in-vitro are different. In the present study, the effects of ketamine and MK-801 on the induction of long-term potentiation (LTP) were compared at perforant path--granule cell synapses in anaesthetized rats. LTP was observed in animals treated with either saline or MK-801, but not in those treated with ketamine. These results reveal that ketamine and MK-801 differentially modulate the induction of LTP, and we propose that this differential modulation may be related to the different binding properties of the drugs.