title: 6-OHDA-induced hemiparkinsonism and chronic L-DOPA treatment increase dopamine D1-stimulated [(3)H]-GABA release and [(3)H]-cAMP production in substantia nigra pars reticulata of the rat.
abstract: It has been proposed that striatonigral GABAergic transmission in the substantia nigra reticulata (SNr) is enhanced during Parkinson's disease and subsequent L-DOPA treatment. To evaluate this proposal we determined the effects of activating dopamine D1 receptors on depolarization induced [(3)H]-GABA release and on [(3)H]-cAMP accumulation in slices of SNr of rats with unilateral 6-OHDA lesions with and without l-DOPA treatment. Denervation increased depolarization induced D1-stimulated [(3)H]-GABA release, while repeated L-DOPA treatment further enhanced this response. Both also enhanced the effects of forskolin on [(3)H]-cAMP production and [(3)H]-GABA release, while neither modified the stimulating effects of 8-Br-cAMP on the release. These results shown that, after 6-OHDA lesions and l-DOPA treatment, cAMP signaling is enhanced. Furthermore, the results suggest that activation of sites in the signaling cascade downstream of cAMP synthesis is not required to increase release.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias. Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional. Apartado Postal 14-740, 07000 México D.F. México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Barajas
authors.forename: Isaac
authors.initials: I
authors.lastname: Silva
authors.forename: Martha
authors.initials: M
authors.lastname: García-Ramírez
authors.forename: Enrique
authors.initials: E
authors.lastname: Sánchez-Lemus
authors.forename: Leonor
authors.initials: L
authors.lastname: Floran
authors.forename: Jorge
authors.initials: J
authors.lastname: Aceves
authors.forename: David
authors.initials: D
authors.lastname: Erlij
authors.forename: Benjamín
authors.initials: B
authors.lastname: Florán
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D007839:Functional Laterality / Q000502:physiology*; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D010726:Phosphodiesterase Inhibitors; D017447:Receptors, Dopamine D1; D014316:Tritium; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine