3H-dopamine uptake and 3H-haloperidol binding in striatum after administration of methyl mercury to rats.
Methyl mercury inhibits dopamine (DA) and serotonin (5-HT) uptake by brain synaptosomes and decreases antagonist binding to striatal dopaminergic D2 receptors in vitro. To assess the effects in vivo, adult rats were given methyl mercury, either as a single dose (10 mg/kg by gavage) or a cumulative total dose of 50 mg/kg in 2 weeks. The repeated dosing decreased body weight and caused neuromuscular dysfunction. In spite of this overt toxicity, neither 3H-DA uptake nor 3H-haloperidol binding changed in striatal synaptosomes. There were no significant alterations in 3H-5-HT uptake by hypothalamic synaptosomes or 3H-flunitrazepam binding in cerebellar synaptosomes. The results suggest that monoaminergic synapses and the benzodiazepine binding sites, associated with cerebellar GABA receptors, remain functionally normal at doses of methyl mercury that are otherwise toxic. The results also emphasize the importance of due care when extrapolating cellular or biochemical data to the level of the whole organism.
D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D006220:Haloperidol / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D008767:Methylmercury Compounds; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D012701:Serotonin; D005445:Flunitrazepam; D006220:Haloperidol; D004298:Dopamine