Effect of the competitive NMDA antagonist, CGP 40 116, and a low dose of l-Dopa on the motor activity deficit of MPTP-treated mice.
Three experiments were performed to investigate the effects of combining the active D-stereoisomer of CGP 37 849, i.e. the glutamatergic antagonist, CGP 40 116, with l-dopa, in mice that had undergone treatment with the neurotoxin, MPTP. In the first experiment, the decreased motor activity in MPTP-treated mice was alleviated by the administration of a low dose of l-dopa (5mg/kg, s.c.) together with a low dose of CGP 40 116 (30µg/kg). This dose was inactive in the control (saline-treated) mice. The highest dose of CGP 40 116 used (3000µg/kg) stimulated activity in the control mice. In Experiment 2, the inactive L-stereoisomer, i.e., CGP 40 117, was found to be inactive at doses (3 and 30µg/kg) effective with CGP 40 116. The effects of CGP 40 116 and l-dopa on the 24-h activity of mice tested under either day-night or night-day conditions, were more marked and longer lasting in the night-day condition. Taken together, the results from all three experiments show that CGP 40 116 in a dose range of 1-30µg/kg in combination with l-dopa (5mg/kg, s.c.) alleviated the reduced motor activity in MPTP-treated mice whereas higher doses of CGP 40 116 (100, 300, or 3000µg/kg) or lower doses (0.1 and 0.3µg/kg) were without effect. These experiments are interpreted as support for current views on glutamatergic-dopaminergic interactions in Parkinsonism and offer further evidence for the MPTP mouse model of the disease.
University of Uppsala, Department of Psychiatry, Ulleråker, S-750 17 Uppsala, Sweden.
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Fredriksson
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Gentsch
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Archer