Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic L-DOPA treatment
Section snippets
Subjects
Female Sprague–Dawley rats (BK Universal, Stockholm, Sweden; 200–225 g body weight at the beginning of the experiments) were housed under a 12 h light/dark cycle with free access to food and water. All rats included in the present study sustained unilateral injections of 6-OHDA in the ascending DA fibre bundle six to eight weeks prior to initiation of the L-DOPA (or saline) treatment. The experimental procedures used were in accordance with the rules laid down by the Swedish authorities. All
Effects of 6-hydroxydopamine lesions, acute or chronic L-DOPA treatment on striatal FosB-like immunoreactivity
On the side of the striatum contralateral to the 6-OHDA lesion, FosB-like-immunoreactive cells were sparse, and confined to the NAc and medial portion of the CPu (Fig. 1A). L-DOPA administration did not have any effect on either the pattern or the overall levels of FosB-like immunoreactivity in the intact striatum. Therefore, only the side of the striatum ipsilateral to the 6-OHDA lesion was considered for quantitative analyses and statistical comparisons. The 6-OHDA lesion alone produced an
Discussion
In the present study we have compared the patterns of FosB-JunB expression produced in the DA-denervated striatum by acute or chronic L-DOPA treatment, and performed a thorough quantitative analysis of striatal FosB-like immunoreactivity. Both acute and chronic treatment with L-DOPA caused a pronounced, persistent increase in the number of FosB-like positive cells (five- and seven-fold increase, respectively, above the levels found in 6-OHDA-lesioned, non-drug-treated controls), but the two
Conclusions
Working on a rat model of Parkinson's disease, we have shown that both DA denervation and DA replacement by L-DOPA induce the expression of JunB and FosB-related proteins in striatal neurons, but that the regional and compartmental distribution of these proteins is markedly different under each condition. Since distinct functions have been associated with different striatal subregions and compartments, these data suggest that striatal FosB-JunB expression has different functional implications
Acknowledgments
We warmly thank Mehrdad Shamloo, Elisabetta Vaudano, Luciano Conti and Massimo DeFraja, for helpful discussion and support concerning the Western blot technique, and Deniz Kirik for his support concerning computer-guided stereology. The excellent technical assistance of Gertrude Stridsberg, Ulla Jarl and Alicja Flash is gratefully acknowledged. This work was supported by grants from the Tore Nilson's Foundation for Medical Research, Åke Wiberg's Foundation, Greta and Johan Kock's Foundations,
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