Summary.
C57/BL6 mice were administered either 7.5 mg Fe2+/kg or vehicle (saline) postnatally on days 10–12 after birth. From 61 days of age onwards for 21 days, groups of mice were administered either clozapine (1 or 5 mg/kg, s.c.) or haloperidol (1 mg/kg, s.c.) or vehicle (Tween-80). Twenty-four hours after the final injection of either neuroleptic compound or vehicle, spontaneous motor activity was measured over a 60-min interval. Following this, each animal was removed, injected apomorphine (1 mg/kg, s.c.) and replaced in the same test chamber. It was found that postnatal administration of Fe2+ at the 7.5 mg/kg dose level reduced activity during the initial 20-min periods (0–20 and 20–40 min) and then induced hyperactivity during the final 20-min period over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hypoactivity in by postnatal Fe2+ during the 1st two 20-min periods over all three parameters of activity. Subchronic treatment with the higher, 5 mg/kg, dose of clozapine abolished or attenuated the hyperactivity in by postnatal Fe2+ during the 3rd and final 20-min period. Subchronic administration of haloperidol, without postnatal iron, increased the level of both locomotion (1st 20 min) and rearing (2nd 20 min) activity. Postnatal administration of Fe2+ at the 7.5 mg/kg dose increased the levels of both locomotion and rearing, but not total activity, following administration of apomorphine (1 mg/kg). Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, reduced the increased locomotor activity caused by postnatal Fe2+, whereas clozapine, 5 mg/kg, elevated further the postnatal Fe2+-induced increased in rearing. Subchronic administration of clozapine, at both the 1 and 5 mg/kg doses, and haloperidol, 1 mg/kg, increased the level of locomotor following administration of apomorphine (1 mg/kg) in mice treated postnatally with vehicle, whereas only clozapine increased the level of rearing. Correlational analyses indicated that both apomorphine-induced locomotion and rearing were highly correlated with the total iron content in the basal ganglia, thereby offering direct evidence of the linear relationship between iron content in the basal ganglia and the behavioural expression of DA D2-receptor supersensitivity in mice.
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Fredriksson, A., Eriksson, P. & Archer, T. Postnatal iron-induced motor behaviour alterations following chronic neuroleptic administration in mice. J Neural Transm 113, 137–150 (2006). https://doi.org/10.1007/s00702-005-0307-3
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DOI: https://doi.org/10.1007/s00702-005-0307-3