dizocilpine-maleate and Iron-Overload

Two experiments were performed to investigate the interactive effects of postnatal iron administration and adult MPTP treatment upon the function of C57 Bl/6 mice tested at adult age and to ascertain the possible ameliatory effects of a subthreshold dose of L-Dopa co-administered with different doses of the uncompetitive glutamate antagonist, MK-801. Experiment I indicated that postnatal iron induced marked deficits (hypoactivity), initially, in all three parameters of motor activity at the 5.0 and 7.5 mg/kg doses, and to a lesser extent at the 2.5 mg/kg dose. Later combination with MPTP (2x40 mg/kg) potentiated severely these deficits. During the final period of testing a marked hyperactivity was obtained for the two higher dose groups; this effect was abolished in mice administered MPTP. Experiment II indicated that the deficits in motor activity parameters induced by postnatal iron at 7.5 mg/kg were alleviated in a dose-related manner by the co-administration of the uncompetitive glutamate antagonist, MK-801, with a subthreshold dose of L-Dopa. Postnatal iron (7.5 mg/kg) administration followed by low doses of MPTP (2x20 mg/kg) 3 months later virtually abolished all motor activity. The combination of these compounds increased also the motor activity of mice treated with MPTP (2x20 mg/kg) or mice treated with the combination of postnatal iron and MPTP. The combination of MK-801 with L-Dopa increased locomotor (0.3 mg/kg), rearing (0.1 and 0.3 mg/kg) and total activity (0.3 mg/kg) of iron-treated mice during the initial, hypoactive 30-min period of testing. Locomotor activity (0.1 mg/kg) of MPTP-treated mice was increased too during this period. During the final 30-min period of testing all three parameters of activity (locomotion, 0.3 mg/kg; rearing and total activity, 0.1 and 0.3 mg/kg) were enhanced in the iron-treated mice, locomotion (0.1 mg/kg) and rearing (0.1 mg/kg) in the iron plus MPTP treated mice and only locomotion (0.1 mg/kg) in the MPTP-treated mice. In control mice (vehicle+saline), the higher doses of MK-801 (0.1 and 0.3 mg/kg) enhanced both locomotor and total activity. Analyses of total iron concentration in the frontal cortex and basal ganglia of Fe(2+) and vehicle treated mice indicated that marked elevations basal ganglia iron levels of the 5.0 and 7.5 mg/kg groups, later injected either saline or MPTP, were obtained (Experiment I). In Experiment II, iron concentrations in the basal ganglia were elevated in both the Fe(2+)-sal and F

Topics: Animals; Behavior, Animal; Brain Chemistry; Critical Period, Psychological; Dizocilpine Maleate; Dopamine Agents; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Habituation, Psychophysiologic; Iron; Iron Overload; Levodopa; Locomotion; Male; Mice; Mice, Inbred C57BL; Motor Activity; MPTP Poisoning; Neuroprotective Agents; Time