adenosine-3--5--cyclic-phosphorothioate and Parkinson-Disease

Chronically administered levodopa, the standard treatment for Parkinson's disease, is ultimately associated with disabling alterations in motor response. To evaluate the possible contribution of striatal cAMP-dependent protein kinase A (PKA) signaling pathways to these response modifications, the acute effects of a PKA inhibitor, Rp-cAMPS, on motor response changes attending chronic, twice-daily administration of levodopa were measured in 6-hydroxydopamine lesioned hemi-parkinsonian rats. A single intrastriatal injection of Rp-cAMPS (2.5 or 25 microg) attenuated both the shortened duration and augmented intensity of levodopa-induced turning in a dose dependent manner. Rp-cAMPS completely normalized motor responses to a dopamine D1 agonist (SKF 38392), but had no effect on those to a dopamine D2 agonist (quinpirole). These results suggest that D1 receptor-mediated PKA activation may contribute to the development of the altered motor responses associated with chronic levodopa treatment.

Topics: Animals; Antiparkinson Agents; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopamine Agents; Dopamine Agonists; Dose-Response Relationship, Drug; Enzyme Inhibitors; Levodopa; Male; Motor Activity; Parkinson Disease; Quinpirole; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Dopamine D1; Receptors, Dopamine D2; Rotation; Stereotyped Behavior; Thionucleotides