Title:  Selective modifications in GAD67 mRNA levels in striatonigral and striatopallidal pathways correlate to dopamine agonist priming in 6-hydroxydopamine-lesioned rats
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Issue Date:  2003
Abstract:  The present study investigated long-term alterations in striatal gene expression after single exposure of unilaterally 6-hydroxydopamine-lesioned rats to different dopamine agonists (priming). Rats were primed with the D1 agonist SKF38393 (10 mg/kg), the D2/D3 agonist quinpirole (0.2 mg/kg), the dopamine precursor L-DOPA (50 mg/kg) or with vehicle (drug-naive), and GAD67, dynorphin and enkephalin mRNAs were evaluated in the striatum by in situ hybridization, 3 days after priming. To evaluate GAD67 mRNA in striatonigral and striatopallidal neurons, identified as enkephalin (-) and (+) neurons, double-labelling in situ hybridization was used. Drug-naive lesioned rats showed an increase in GAD67 mRNA in enkephalin (-) and (+) neurons, an increase in enkephalin and a decrease in dynorphin mRNAs. Priming with either SKF38393 or quinpirole further increased GAD67 mRNA in enkephalin (-) and (+) neurons, however, while SKF38393 produced a high and unbalanced activation toward enkephalin (-) neurons, after quinpirole the increase was of low intensity and similar in the two pathways. Dynorphin mRNA was increased by SKF38393 but not by quinpirole, whereas enkephalin mRNA was not changed by either priming. L-DOPA produced a high and similar increase in GAD67 mRNA in enkephalin (-) and (+) neurons. Priming differentially affected peptides and GAD67 mRNA in striatopallidal and striatonigral neurons depending on the dopamine agonist used. The degree of enduring overactivity of the striatopallidal and striatonigral pathways may be related to the ability of L-DOPA and D1 or D2/D3 receptor agonists to prime motor behavioural responses and to produce dyskinetic side-effects.
URI:  http://hdl.handle.net/11584/96896
Type: 1.1 Articolo in rivista

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