Partial lesions of the nigrostriatal pathway in the rat. Acceleration of transmitter synthesis and release of surviving dopaminergic neurones by drugs

F. Hefti, A. Enz, E. Melamed

Research output: Contribution to journalArticlepeer-review

Abstract

In rats with partial, unilateral lesions of the dopaminergic nigrostriatal pathway, synthesis of dopamine (DA) per surviving neurone was assessed by measuring the ratio of DOPA accumulated after inhibition of aromatic amino acid decarboxylase to dopamine ( DOPA DA ratio). Release of DA per surviving neurone was assessed by measuring the ratios of the concentrations of 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) to DA. In striata ipsilateral to the lesion, the DOPA DA ratio was elevated 4-fold, and the DOPA DA and HVA DA ratios were elevated 2-fold as compared to values in contralateral striata. Administration of γ-butyrolacetone (750 mg/kg, 30 min), i.e. of a drug which accelerates synthesis of DA, further increased the DOPA DA ratio in lesioned striata to levels 37 times higher than those measured on the control side of saline-injected controls. Morphine (20 mg/kg, 30 min) and haloperidol (2.5 mg/kg, 60 min), i.e. drugs known to accelerate the turnover and release of DA, further elevated the DOPAC DA and HVA DA ratios in lesioned striata to levels approx. 5 times higher than the ratios measured on contralateral sides of saline-treated controls. The data indicate that dopaminergic neurones surviving partial lesions of the nigrostriatal pathway synthesize and release DA at an elevated but submaximal rate. Synthesis and release of DA can be further enhanced to a large extent by drugs.

Original languageEnglish
Pages (from-to)19-23
Number of pages5
JournalNeuropharmacology
Volume24
Issue number1
DOIs
StatePublished - Jan 1985
Externally publishedYes

Keywords

  • 6-hydroxydopamine
  • Parkinson's disease
  • dopamine
  • haloperidol
  • morphine
  • nigrostriatal neurones
  • partial lesion
  • γ-butyrolactone

Fingerprint

Dive into the research topics of 'Partial lesions of the nigrostriatal pathway in the rat. Acceleration of transmitter synthesis and release of surviving dopaminergic neurones by drugs'. Together they form a unique fingerprint.

Cite this