RT Journal Article SR Electronic T1 Behavioral and Cellular Modulation of l-DOPA-Induced Dyskinesia by β-Adrenoceptor Blockade in the 6-Hydroxydopamine-Lesioned Rat JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 755 OP 765 DO 10.1124/jpet.111.179416 VO 337 IS 3 A1 David Lindenbach A1 Corinne Y. Ostock A1 Karen L. Eskow Jaunarajs A1 Kristin B. Dupre A1 Christopher J. Barnum A1 Nirmal Bhide A1 Christopher Bishop YR 2011 UL http://jpet.aspetjournals.org/content/337/3/755.abstract AB Chronic dopamine replacement therapy in Parkinson's disease (PD) leads to deleterious motor sequelae known as l-DOPA-induced dyskinesia (LID). No known therapeutic can eliminate LID, but preliminary evidence suggests that dl-1-isopropylamino-3-(1-naphthyloxy)-2-propanol [(±)propranolol], a nonselective β-adrenergic receptor (βAR) antagonist, may reduce LID. The present study used the rat unilateral 6-hydroxydopamine model of PD to characterize and localize the efficacy of (±)propranolol as an adjunct to therapy with l-DOPA. We first determined whether (±)propranolol was capable of reducing the development and expression of LID without impairing motor performance ON and OFF l-DOPA. Coincident to this investigation, we used reverse-transcription polymerase chain reaction techniques to analyze the effects of chronic (±)propranolol on markers of striatal activity known to be involved in LID. To determine whether (±)propranolol reduces LID through βAR blockade, we subsequently examined each enantiomer separately because only the (−)enantiomer has significant βAR affinity. We next investigated the effects of a localized striatal βAR blockade on LID by cannulating the region and microinfusing (±)propranolol before systemic l-DOPA injections. Results showed that a dose range of (±)propranolol reduced LID without deleteriously affecting motor activity. Pharmacologically, only (−)propranolol had anti-LID properties indicating βAR-specific effects. Aberrant striatal signaling associated with LID was normalized with (±)propranolol cotreatment, and intrastriatal (±)propranolol was acutely able to reduce LID. This research confirms previous work suggesting that (±)propranolol reduces LID through βAR antagonism and presents novel evidence indicating a potential striatal locus of pharmacological action.