Adult and in utero exposure to cocaine alters sensitivity to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Cocaine abuse is a significant problem in the United States, including its use by approximately 1% of pregnant women. Cocaine acts as an indirect agonist of dopamine at the dopamine transporter, resulting in the presence of excess dopamine in the synapse. Since synaptic dopamine can rapidly oxidize to form free radicals, it was hypothesized that exposure to this drug might produce damage in dopaminergic systems such as the substantia nigra pars compacta, damage to which is a hallmark of Parkinson's disease. To test this hypothesis we exposed mice both in utero and as adults to cocaine and examined its effects on the nigrostriatal system. We found that exposure to cocaine both in utero or as adults did not affect substantia nigra cell number, but did make these neurons more susceptible to the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. We also found long-lasting changes in D2 receptor mRNA levels as well as changes in the monoamine transport system and several growth factors. This work suggests that use of cocaine might be a predisposing factor for development of Parkinson's disease in both adults exposed chronically as well as in individuals exposed prenatally.
Lloyd
S A
SA
Department of Developmental Neurobiology, Saint Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Faherty
C J
CJ
Smeyne
R J
RJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D017931:DNA Primers; D015259:Dopamine Agents / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003042:Cocaine