INTRASTRIATALLY INJECTED C-FOS ANTISENSE OLIGONUCLEOTIDE INTERFERES WITH STRIATONIGRAL BUT NOT STRIATOPALLIDAL GAMMA-AMINOBUTYRIC-ACID TRANSMISSION IN THE CONSCIOUS RAT

Antisense c-fos oligonucleotides injected into the neostriatum of cons cious rats selectively inhibited c-fos expression associated with comp ensatory increases in striatal c-fos mRNA levels and also with Increas ed expression of junB and NGFI-A mRNA, probably as a result of regulat ory phenomena. Dual probe in vivo microdialysis was used to Investigat e gamma-aminobutyric acid (GABA) release in the substantia nigra and t he globus pallidus, which represent the terminal sites of the dopamine D-1 receptor regulated striatonigral and the dopamine D-2 receptor re gulated striatopallidal GABA pathways, respectively. Intrastriatal inf usion of the c-fos antisense oligonucleotide profoundly decreased dial ysate GABA levels in the ipsilateral substantia nigra within 60 min hu t did not influence the dialysate GABA levels in the globus pallidus c ompared 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 fin dings demonstrate a facilitatory role for c-fos mediated gene regulati on in striatonigral GABA transmission and strengthen the evidence that the regulation of neurotransmission is different in the striatonigral and striatopallidal GABA pathways.