Behavioural 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-hydroxydopamine lesioned rats following exposure to a dopamine agonist. After priming, a single dose of the D1 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 D1 receptors in striatum. Dephospho-form of DARPP-32 were 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 D1 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 D1 receptor message.
Department of Neurology, University of Napoli, Italy.
P
P
Barone
M
M
Morelli
M
M
Popoli
G
G
Cicarelli
G
G
Campanella
G
G
Di Chiara
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016627:Oxidopamine; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D013563:Sympathectomy, Chemical
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017447:Receptors, Dopamine D1; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D004298:Dopamine