Subchronic administration of haloperidol influences the functional deficits of postnatal iron administration in mice.
C57/BL6 mice were administered either 7.5 mg Fe(2+) (II)/ kg or vehicle (saline) postnatally on Days 10-12 after birth. From 64 days of age onwards for 24 days, groups of mice were administered either haloperidol (0.25 or 1 or 2 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. Postnatal Fe(2+)-treatment (7.5 mg/kg, postnatally) reduced motor activity parameters 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, confirming previous observations. Subchronic administration of haloperidol, at the 1 and 2 mg/kg doses, and to a lesser extent the 0.25 mg/kg dose, increased the levels of activity in all three motor activity parameters in postnatal iron-treated mice: locomotion (1st and 2nd 20 min periods), rearing (1st and 2nd 20 min periods) and total activity (1st 20 min period). All three doses of haloperidol abolished the later hyperactivity in iron-treated mice, with the exception of the 0.25 mg/kg dose with regard to rearing behaviour. Apomorphine (1 mg/kg, s.c.)-induced activity was elevated by postnatal iron administration and by subchronic administration of apomorphine at the higher dose levels. In the context of these and other observations, it is suggested that subchronic administration of haloperidol interacting with postnatal iron induces different expressions of dopamine neuron comorbidity underlying movement disorder.
Fredriksson
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A
University of Uppsala, Department of Neuroscience and Psychiatry, Ulleraker, SE-750 17 Uppsala, Sweden.
Archer
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T
D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage*; D007501:Iron / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D013223:Statistics as Topic; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007501:Iron; D006220:Haloperidol; D001058:Apomorphine