title: Microtopography of D1 dopaminergic binding sites in the human substantia nigra: an autoradiographic study.
abstract: The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.
authors.affiliation: INSERM U289, Hôpital de la Salpêtrière, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Thibaut
authors.forename: E C
authors.initials: EC
authors.lastname: Hirsch
authors.forename: R
authors.initials: R
authors.lastname: Raisman
authors.forename: F
authors.initials: F
authors.lastname: Javoy-Agid
authors.forename: Y
authors.initials: Y
authors.lastname: Agid
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000473:pathology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008636:Mesencephalon / Q000201:enzymology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D013378:Substantia Nigra / Q000033:anatomy & histology* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase