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Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal gamma-aminobutyric acid transmission in the conscious rat

Item Type:Article
Title:Intrastriatally injected c-fos antisense oligonucleotide interferes with striatonigral but not striatopallidal gamma-aminobutyric acid transmission in the conscious rat
Creators Name:Sommer, W. and Rimondini, R. and O'Connor, W. and Hansson, A. and Ungerstedt, U. and Fuxe, K.
Abstract:Antisense c-fos oligonucleotides injected into the neostriatum of conscious rats selectively inhibited c-fos expression associated with compensatory increases in striatal c-fos mRNA levels and also with increased expression of junB and NGFI-A mRNA, probably as a result of regulatory phenomena. Dual probe in vivo microdialysis was used to investigate gamma-aminobutyric acid (GABA) release in the substantia nigra and the globus pallidus, which represent the terminal sites of the dopamine D1 receptor regulated striatonigral and the dopamine D2 receptor regulated striatopallidal GABA pathways, respectively. Intrastriatal infusion of the c-fos antisense oligonucleotide profoundly decreased dialysate GABA levels in the ipsilateral substantia nigra within 60 min but did not influence the dialysate GABA levels in the globus pallidus compared with the sham and control oligonucleotide treated groups. The site of action of the antisense oligonucleotides was mainly restricted to striatal neurons as shown by the distribution of locally injected fluoresceine isothiocyanate and radiolabeled oligonucleotides. The findings demonstrate a facilitatory role for c-fos mediated gene regulation in striatonigral GABA transmission and strengthen the evidence that the regulation of neurotransmission is different in the striatonigral and striatopallidal GABA pathways.
Keywords:Phosphorothioate Oligonucleotides, Microdialysis, Dopamine Receptors, Motor Circuit, Animals, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:93
Number:24
Page Range:14134-14139
Date:26 November 1996
Official Publication:http://www.pnas.org/content/93/24/14134.abstract
PubMed:View item in PubMed

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