The effects of lead administration during development on lithium-induced polydipsia and dopaminergic function.
Previous studies have demonstrated that postnatal (days 2-29 of life) administration of lead (200 mg/kg/day by gavage) to Long-Evans rats caused permanent increases in lithium-induced polydipsia (LIP). These lead-induced increases in LIP were apparently not of renal origin, did not occur in animals treated with lead after day 30, and persisted for at least 6 months. The present studies have narrowed the dose-time window for lead-induced increases in LIP. The first study showed that continuous administration of lead (200 mg/kg/day, p.o.) in the form of lead acetate during days 2-9 of life caused increases in LIP (P = 0.022). Although lead-induced increases in LIP were not statistically significant (P = 0.084) for the group administered lead from days 9 to 19, the lack of a significant difference between the 2-9- and 9-19-day groups suggested that lead treatment during either of these time periods would result in LIP increases. Lead administration between days 19 and 29 of life was not effective in increasing LIP (P = 0.8). In the second study, a single dose of lead (200 mg/kg/day) was administered either on day 5 or 15 of life. Concentrations of lead in the blood on day 30 of life averaged 23.2 micrograms/100 ml for treated rats versus 4.8 micrograms/100 ml for controls. When tested at approximately 90 days of age, both groups showed significant increases in LIP (P = 0.028). The rats from this second study were also examined for changes in nigrostriatal dopamine function, since this pathway is known to be essential for LIP.(ABSTRACT TRUNCATED AT 250 WORDS)
D000367:Age Factors; D000818:Animals; D002712:Chlorides / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D005260:Female; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D009942:Organometallic Compounds; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D002712:Chlorides; D009942:Organometallic Compounds; D011954:Receptors, Dopamine; D007854:Lead; D013134:Spiperone; D008094:Lithium; D018021:Lithium Chloride; C008261:lead acetate; D004298:Dopamine