Antagonists of N-methyl-d-aspartate receptor partially prevent the development of cocaine sensitization

Behavioral sensitization to cocaine was tested for in rats pretreated with MK-801, a noncompetitive ^À/-methyl-D-aspartate (NMDA) receptor antagonist, or D-3-(2-carborypiperaan-4-yl)-l-propenyl-l-phosphonic acid (D-CPPene), a competitive NMDA antagonist. A 5-day regimen of once-daily ssç¡ine (15 mglkg) injections yielded sensitization to cocaine (15 mglkg)-induced behavioral activation. Cocaine sensitiz¿tion lilas partially prevented by MK-801 (0.25 m/kg) or D-CPPene (2A mdks) pretreatment. These rezults differ from previous reports that NMDA receptor antagonists completely prevented tåe development of stimulant sensitization. While raising questions about methodological differences among laboratories studying this iszue, our findings suggest that sensitization may involve mechanisms dependent on NMDA-receptor function as well as NMDA receptor-independent mechanisms