Neurotoxicity Research

, Volume 11, Issue 3, pp 169–182

Exploring neurocircuitries of the basal ganglia by intracerebral administration of selective neurotoxins

  • Mario Herrera-Marschitz
  • Diego Bustamante
  • Paola Morales
  • Michel Goiny
Article

DOI: 10.1007/BF03033566

Cite this article as:
Herrera-Marschitz, M., Bustamante, D., Morales, P. et al. neurotox res (2007) 11: 169. doi:10.1007/BF03033566

Abstract

The detailed anatomy of the monoamine pathways of the rat, first described by the students of Nils-Åke Hillarp in Sweden, provided the basis for a neurocircuitry targeted pharmacology, leading to important therapeutic breakthroughs. Progress was achieved by the introduction of accurate lesion techniques based on selective neurotoxins. Systematic intracerebral injections of 6-hydroxydopamine let Urban Ungerstedt at the Karolinska Institutet, Stockholm, Sweden, to propose the first stereotaxic mapping of the monoamine pathways in the rat brain; and the ‘Rotational Behaviour’, as a classical model for screening drugs useful for alleviating Parkinson’s disease and other neuropathologies. The direction of the rotational behaviour induced by drugs systematically administrated to unilaterally 6-hydroxydopamine-lesioned rats reveals their mechanism of action at dopamine synapses, as demonstrated when rotational behaviour was combined with microdialysis. The model was useful for proposing a role of dopamine receptors in the gating of the flow of information integrated and/or modulated by the basal ganglia, through different efferent pathways; notably the striatopallidal system, via D2 receptors, and the striatonigral system, via D1 receptors. The role of other dopamine receptor subtypes on rotational behaviour has not yet been clarified.

Keywords

AmphetamineApomorphineBasal gangliaRotational behaviourMicrodialysisRat

Copyright information

© Springer 2007

Authors and Affiliations

  • Mario Herrera-Marschitz
    • 1
  • Diego Bustamante
    • 1
  • Paola Morales
    • 1
  • Michel Goiny
    • 2
  1. 1.Programme of Molecular & Clinical Pharmacology, ICBM, Medical FacultyUniversity of Chile, SantiagoChile
  2. 2.Department of Physiology & PharmacologyKarolinska InstitutetStockholmSweden