Effects of prenatal exposure to methylmercury on dopamine-mediated locomotor activity and dopamine D2 receptor binding.
In the present study we have investigated the neurotoxic effects of the exposure to a low dose (0.5 mg/kg/day) of methylmercury (MeHg) on the developing nervous system. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. At postnatal day 20 the offspring did not display prominent functional cerebellar alterations, as evaluated by the Rotarod performance. Motor activity (locomotion, rearing and motility) was tested in the 21-day-old rats after administration of apomorphine, an agonist of D(1), D(2), and D(3) dopamine receptors. A low dose of apomorphine (0.1 mg/kg) induced a significantly stronger increase in motility and locomotion in MeHg-treated rats as compared to controls. The same effect was also observed in rats injected with 1 mg/kg apomorphine. No changes were observed in rearing at either doses of the dopamine receptor agonist. The data suggest that changes in dopaminergic transmission are induced by exposure to MeHg in early life. The expression of the striatal dopamine D(1) and D(2) receptors was examined by in situ hybridization in the striatum of the 21-day-old rats. The analysis did not reveal any significant changes at the mRNA level. Ligand autoradiography experiments showed a significant reduction in dopamine D(2) receptor binding in the caudate putamen of MeHg-treated rats. Spatial learning ability was tested in 2-month-old rats using the Morris swim maze test. Changes in retention were shown in MeHg-treated rats, indicating that MeHg induced memory alterations. Taken together, these findings show that exposure to a very low dose of MeHg during development exerts neurotoxic effects on the dopaminergic system and that alterations of brain functions persist in adult life.
Daré
Elisabetta
E
Institute of Environmental Medicine, Division of Toxicology and Neurotoxicology, Karolinska Institutet, 171 77 Stockholm, Sweden. Elisabetta.Dare@fyfa.ki.se
Fetissov
Serguei
S
Hökfelt
Tomas
T
Hall
Håkan
H
Ogren
Sven Ove
SO
Ceccatelli
Sandra
S
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001058:Apomorphine / Q000008:administration & dosage / Q000493:pharmacokinetics; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D005260:Female; D017403:In Situ Hybridization; D018782:Maze Learning / Q000187:drug effects; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test; D013550:Swimming
D008767:Methylmercury Compounds; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine; D004298:Dopamine