SYNERGISTIC EFFECTS OF COCAINE AND DIZOCILPINE (MK-801) ON BRAIN-STIMULATION REWARD

The rewarding effects of lateral hypothalamic electrical stimulation w ere assessed in animals treated with the combination of cocaine and di zocilpine (MK-801), a noncompetitive N-methyl-D-aspartate antagonist. Eight male Long-Evans rats were trained to perform a lever-press opera nt to deliver trains of cathodal rectangular pulses directly into the lateral hypothalamus. Response rate was determined across the range of effective stimulation frequencies. For each rat the frequency thresho ld was defined as the lowest frequency that sustained minimal respondi ng. After thresholds had stabilized each rat was tested under 4 treatm ent conditions; saline + saline, dizocilpine (0.05 mg/kg, i.p., 30 min before test) + saline, saline + cocaine (4 mg/kg, i.p., 5 min before test) and dizocilpine + cocaine. The saline + saline, dizocilpine + sa line and saline + cocaine treatments each failed to cause significant changes in threshold or maximum response rates. The dizocilpine + coca ine treatment produced a large reduction in thresholds indicating a sy nergism between the two drugs and the rewarding stimulation. These syn ergistic effects of dizocilpine and cocaine stand in contrast to the p utative antagonism by dizocilpine of cocaine's psychomotor-sensitizing action.