BEHAVIORAL SENSITIZATION IN 6-HYDROXYDOPAMINE LESIONED RATS INVOLVES THE DOPAMINE SIGNAL-TRANSDUCTION - CHANGES IN DARPP-32 PHOSPHORYLATION

''Priming'' is a phenomenon of behavioural sensitization observed in unilaterally 6-hydroxy-dopamine lesioned rats following exposure to a dopamine agonist. After priming, a single dose of the D-1 agonist SKF 38393 (3 mg/kg) produces contralateral turning, while the same dose is inactive in drug-naive, lesioned animals. The molecular mechanisms of ''priming'' were investigated here by studying the phosphorylation of dopamine and adenosine 3'-5' monophosphate regulated phosphoprotein (DARPP-32), a dopamine- and cyclic AMP-regulated phosphoprotein functionally linked to D-1 receptors in striatum. Dephospho-form of DARPP-32 was measured by a back-phosphorylation assay. All assays were performed in striata from both lesioned and unlesioned sides. A significant decrease of dephospho-DARPP-32 (27%) was observed in the denervated striatum of primed rats, indicating an increased phosphorylation in vivo of DARPP-32 in response to the D-1 agonist. The levels of DARPP-32 protein. as measured by quantitative immunoblotting, remained unchanged in all experimental groups. This study shows that priming is expressed as an increased transduction of the D-1 receptor message.