l-Dopa and brown fat hemorrhage in the rat pup

Female Sprague-Dawley rats were given l-dopa during gestation. Several hours after birth, hemorrhages appeared in the interscapular brown adipose tissue of some of the offspring of l-dopa treated rats. Histological examination of the brown fat of these pups showed large hemorrhages and vasodilation. Administration of l-dopa during the first 5 days of gestation and dopamine for the first 7 days of gestation caused a dose-related occurrence of hemorrhage in the offspring. Cross-foster experiments demonstrated that pups exposed to l-dopa in utero had a significantly increased chance of hemorrhage, while pups nursed by l-dopa-treated rats did not. During Days 1–21 of gestation, haloperidol (1 mg/kg/day) partially blocked the effect of l-dopa (100 mg/kg/day) while propranolol (5 mg/kg/day) and phenoxybenzamine (10 mg/kg/day) did not. When given with l-dopa, the decarboxylase inhibitors MK 486 and RO 4–4602 reduced the frequency of hemorrhages. The combination of l-dopa (100 mg/kg), pyrogallol (100 mg/kg), and tranylcypromine (1.5 mg/kg) produced 20.8% hemorrhage in the pups, a significant increase compared to l-dopa (100 mg/kg) alone (7.9%). Among eight different amino acids and amines tested, dopamine was the most hemorrhagic. The dopamine-β-hydroxylase inhibitor, dimethyldithiocarbamate (125 mg/kg), given daily for the first 7 days of gestation, led to brown fat hemorrhage in 17.6% of the offspring, suggesting that dopamine may be implicated in this effect.