SYSTEMIC PRETREATMENT WITH MK-801 (DIZOCILPINE) INCREASES BREAKING POINTS FOR SELF-ADMINISTRATION OF COCAINE ON A PROGRESSIVE-RATIO SCHEDULE IN RATS

The effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, on cocaine self-administration were investigated. Forty-six male Wistar rats were trained to intravenously self-adminis ter four unit doses of cocaine (0.19, 0.38, 0.75 and 1.5 mg/kg per inj ection) on a progressive-ratio schedule of reinforcement. The effects of increasing doses of MK-801 (0.05, 0.1, 0.15 and 0.2 mg/kg, IP, 30 m in before test sessions) on breaking point (BP) for cocaine self-admin istration were investigated. The results showed that pretreatment with MK-801 produced effects on cocaine BPs that fit on an inverted-U func tion. That is, the 0.05 and 0.1 mg/kg doses of MK-801 produced no effe ct or a small enhancement of BPs across all doses of cocaine, respecti vely. The 0.15 mg/kg dose of MK-801 produced a significant treatment e ffect characterized by increased BPs, relative to baseline BPs, across all doses of cocaine. The 0.2 mg/kg dose of MK-801 produced a nonsign ificant decrease in BPs across most doses of cocaine. The dose-depende nt effects on cocaine BPs after pretreatment with MK-801 suggest that MK-801 can potentiate and at higher doses attenuate, the rewarding eff ects of self-administered cocaine.