Dizocilpine (MK-801), ketamine and phencyclidine: low doses affect brain field potentials in the freely moving rat in the same way as activation of dopaminergic transmission

Abstract

The effects of dizocilpine (MK-801), (±)-5-methyl-10,11-dihydro-5Hdibenzo-[a,d]-cyclohepten-5,10-imine maleate, after IP injection into freely behaving rats, have been compared with the action of ketamine-chloride and phencyclidine (PCP). MK-801 produced strongly dose-dependent effects which could be followed quantitatively over a time of 4 h. During this time spectral analysis of the field potentials continuously recorded from frontal cortex, hippocampus, striatum, and reticular formation revealed a particular pattern of changes which was very stable over time, and, after low doses of 0.05 and 0.1 mg/kg, matched that produced by phencyclidine (2 and 4 mg/kg) or ketamine chloride (10 and 20 mg/kg). With higher doses of MK-801 a continuous change from power decreases to power increases was observed. These increases were accompanied by strong behavioral effects in terms of impaired locomotor control. All three non-competitive NMDA antagonists showed a high degree of similarity with respect to the changes of the frequency content of the field potentials over time. The same pattern of electrical changes could be observed after the application ofl-dopa (50 mg/kg) or amphetamine (0.2 mg/kg). This can be interpreted in the sense that the same population of cells within the recording area which is under dopaminergic control is at the same time under glutamate control. This leads to the hypothesis that it might be possible to bypass the missing dopaminergic control during parkinsonism by noncompetitive NMDA-receptor blocking drugs.