Exploring neurocircuitries of the basal ganglia by intracerebral administration of selective neurotoxins.
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.
Herrera-Marschitz
Mario
M
Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago, Chile. mh-marschitz@med.uchile.cl
Bustamante
Diego
D
Morales
Paola
P
Goiny
Michel
M
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
D009498:Neurotoxins; D011954:Receptors, Dopamine