Degeneration of pre-labelled nigral neurons induced by intrastriatal 6-hydroxydopamine in the rat: behavioural and biochemical changes and pretreatment with the calcium-entry blocker nimodipine

Exp Brain Res. 1997 Oct;117(1):111-9. doi: 10.1007/s002210050204.

Abstract

Intrastriatal application of 6-hydroxydopamine (6-OHDA) initiates a delayed and progressive loss of nigral dopaminergic neurons and therefore may better resemble the slowly developing neuropathology of Parkinson's disease. We investigated the anatomical, behavioural and biochemical consequences of intrastriatal 6-OHDA after prior labelling of nigral dopaminergic neurons in rats and whether the dihydropyridine L-type calcium channel blocker nimodipine protected from the induced deficits. Adult rats received bilateral intrastriatal injections of the retrograde fluorescence tracer fluorogold and nimodipine (n=12) or placebo (n=9) pellets implanted subcutaneously. One week later all rats were injected unilaterally with 6-OHDA (20 microg) at the same intrastriatal site. Placebo-treated rats displayed relatively few d-amphetamine-induced ipsilateral net rotations (R) (1.3+/-1.4 R/min; mean+/-SEM) 1 week after the lesion with a slight but non-significant decline thereafter (after 2, 3 and 4 weeks). In nimodipine-treated rats the rotation behaviour after 1 week was more prominent (3.5+/-0.8 R/min; mean+/-SEM) with a similar slight decline until week 4. Fluorescent and immunocytochemical analysis of the midbrain after 4 weeks revealed a 35% and 39% loss of tyrosine hydroxylase positive cells and a 62% and 56% (placebo and nimodipine, respectively) loss of fluorogold-labelled cells in the ipsilateral substantia nigra pars compacta. Striatal dopamine levels were reduced to 47% (placebo) and 43% (nimodipine) of the control side and the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid to about 50%. Pretreatment with nimodipine failed to antagonize or to ameliorate any of the lesion-induced deficits. We conclude that pretreatment with 80 mg nimodipine pellets does not prevent nigrostriatal damage induced by intrastriatal 6-OHDA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Calcium Channel Blockers / pharmacology*
  • Dopamine / metabolism
  • Female
  • Immunohistochemistry
  • Injections
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Nimodipine / pharmacology*
  • Oxidopamine / administration & dosage
  • Oxidopamine / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Rotation
  • Substantia Nigra / cytology*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Sympatholytics / administration & dosage
  • Sympatholytics / toxicity*

Substances

  • Calcium Channel Blockers
  • Sympatholytics
  • Nimodipine
  • Oxidopamine
  • Dopamine