title: Gamma-aminobutyric acid(B) autoreceptors in substantia nigra and neostriatum of the weaver mutant mouse.
abstract: The weaver mutation causes cell loss in the center of the substantia nigra, pars compacta. We compared the depression of gamma-aminobutyric acid (GABA)(A) synaptic currents by the GABA(B) agonist R-baclofen in pars compacta neurons of weaver mice which were largely spared from cell degeneration and of wild-type mice. In weaver neurons the suppression of GABA(A) synaptic currents by R-baclofen was reduced compared to wild-type neurons. The EC(50) of R-baclofen was 6.3 times higher in weaver than in wild-type mice. In the neostriatum, which is not a target of the mutation, such a difference did not exist. We conclude that in the pars compacta the weaver mutation leads to a reduced presynaptic autoinhibition through GABA(B) receptors which may promote survival of a subset of weaver neurons in the pars compacta.
authors.affiliation: Institut für Physiologie und Pathophysiologie, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Radnikow
authors.forename: S
authors.initials: S
authors.lastname: Titz
authors.forename: S
authors.initials: S
authors.lastname: Mades
authors.forename: J
authors.initials: J
authors.lastname: Bäurle
authors.forename: U
authors.initials: U
authors.lastname: Misgeld
mesh_terms: D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D017660:Autoreceptors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D001418:Baclofen; D004298:Dopamine