Synergistic effects of cocaine and dizocilpine (MK-801) on brain stimulation reward

The rewarding effects of lateral hypothalamic electrical stimulation were assessed in animals treated with the combination of cocaine and dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate antagonist. Eight male Long-Evans rats were trained to perform a lever-press operant 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 threshold was defined as the lowest frequency that sustained minimal responding. After thresholds had stabilized each rat was tested under 4 treatment 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 + saline and saline + cocaine treatments each failed to cause significant changes in threshold or maximum response rates. The dizocilpine + cocaine treatment produced a large reduction in thresholds indicating a synergism between the two drugs and the rewarding stimulation. These synergistic effects of dizocilpine and cocaine stand in contrast to the putative antagonism by dizocilpine of cocaine's psychomotor-sensitizing action.