The adaptation of enkephalin, tachykinin and monoamine neurons of the basal ganglia following neonatal dopaminergic denervation is dependent on the extent of dopamine depletion

Brain Res. 1990 Dec 17;536(1-2):169-75. doi: 10.1016/0006-8993(90)90022-4.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Adaptation, Physiological / physiology*
  • Animals
  • Animals, Newborn / physiology*
  • Basal Ganglia / drug effects
  • Basal Ganglia / physiology*
  • Biogenic Monoamines / physiology
  • Chromatography, High Pressure Liquid
  • Denervation
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Enkephalin, Methionine / genetics
  • Enkephalin, Methionine / physiology
  • Female
  • Hydroxydopamines
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Neurons / physiology*
  • Nucleic Acid Hybridization
  • Oxidopamine
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Substance P / genetics
  • Substance P / physiology

Substances

  • Biogenic Monoamines
  • Hydroxydopamines
  • RNA, Messenger
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Substance P
  • Hydroxyindoleacetic Acid
  • Enkephalin, Methionine
  • Oxidopamine
  • Dopamine