title: Exploring neurocircuitries of the basal ganglia by intracerebral administration of selective neurotoxins.
abstract: The detailed anatomy of the monoamine pathways of the rat, first described by the students of Nils Ake 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 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 for 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 D(2) receptors, and the striatonigral system, via D(1) receptors. The role of other dopamine receptor subtypes on rotational behaviour has not yet been clarified.
authors: Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago, Chile. mh-marschitz@med.uchile.cl
authors: Mario
authors: M
authors: Herrera-Marschitz
authors: Diego
authors: D
authors: Bustamante
authors: Paola
authors: P
authors: Morales
authors: Michel
authors: M
authors: Goiny
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D049673:History, 20th Century; D006801:Humans; D009415:Nerve Net / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000008:administration & dosage* / Q000266:history; D011954:Receptors, Dopamine / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D011954:Receptors, Dopamine