6-OHDA-induced hemiparkinsonism and chronic l

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• 作者：Claudia Rangel-Barajas ; Isaac Silva ; Martha Garcí ; a-Ramí ; rez ; Enrique Sá ; nchez-Lemus ; Leonor Floran ; Jorge Aceves ; David Erlij ; Benjamí ; n Florá ; n
• 关键词：l-DOPA ; Basal ganglia ; GABA release ; cAMP ; Hemiparkinsonism ; Substantia nigra
• 刊名：Neuropharmacology
• 出版年：2008
• 出版时间：October 2008
• 年：2008
• 卷：55
• 期：5
• 页码：704-711
• 全文大小：909 K

文摘

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 [³H]-GABA release and on [³H]-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 [³H]-GABA release, while repeated l-DOPA treatment further enhanced this response. Both also enhanced the effects of forskolin on [³H]-cAMP production and [³H]-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.