title: The adaptation of enkephalin, tachykinin and monoamine neurons of the basal ganglia following neonatal dopaminergic denervation is dependent on the extent of dopamine depletion.
abstract: This study examined whether dopamine (DA) is necessary for the normal development of striatal enkephalin and striatonigral tachykinin peptide systems. The neurotoxin, 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on the third day of the postnatal period in Sprague-Dawley rat pups. The animals were sacrificed at 60 days of age. The levels of Met5-enkephalin (ME) and substance P (SP) were determined by radioimmunoassay and preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the striatum were assessed by hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT) and their acid metabolites were determined by high-pressure liquid chromatography with electrochemical detection. The lesioned animals were grouped on the basis of the degree of loss of DA, and changes in ME, SP and 5-HT systems were correlated with respect to the degree of DA loss. The nature and extent of the changes in these systems were dependent on the degree of DA depletion. A loss of more than 90% DA was necessary to result in increased levels of ME and its PPE mRNA and reduced levels of SP and its PPT mRNAs; however, increased levels of 5-HT could be observed at a lower degree of DA loss. The results indicate that the normal development of enkephalin and tachykinin and 5-HT systems of basal ganglia are dependent on the availability of DA and/or the integrity of the nigrostriatal dopaminergic neurons. The results are relevant to our further understanding of the neurobiology of DA deficiency disorders.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Gary 46408.
authors.forename: S P
authors.initials: SP
authors.lastname: Sivam
authors.forename: J E
authors.initials: JE
authors.lastname: Krause
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D015306:Biogenic Monoamines / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003714:Denervation; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000235:genetics / Q000502:physiology; D005260:Female; D006892:Hydroxydopamines; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D016627:Oxidopamine; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013373:Substance P / Q000235:genetics / Q000502:physiology
chemical_list: D015306:Biogenic Monoamines; D006892:Hydroxydopamines; D012333:RNA, Messenger; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D013373:Substance P; D006897:Hydroxyindoleacetic Acid; D004744:Enkephalin, Methionine; D016627:Oxidopamine; D004298:Dopamine