title: Effects of noradrenergic denervation on L-DOPA-induced dyskinesia and its treatment by α- and β-adrenergic receptor antagonists in hemiparkinsonian rats.
abstract: While L-3,4-dihydroxyphenylalanine (L-DOPA) remains the standard treatment for Parkinson's disease (PD), long-term efficacy is often compromised by L-DOPA-induced dyskinesia (LID). Recent research suggests that targeting the noradrenergic (NE) system may provide relief from both PD and LID, however, most PD patients exhibit NE loss which may modify response to such strategies. Therefore this investigation aimed to characterize the development and expression of LID and the anti-dyskinetic potential of the α2- and β-adrenergic receptor antagonists idazoxan and propranolol, respectively, in rats receiving 6-OHDA lesions with (DA lesion) or without desipramaine protection (DA+NE lesion). Male Sprague-Dawley rats (N=110) received unilateral 6-hydroxydopamine lesions. Fifty-three rats received desipramine to protect NE neurons (DA lesion) and 57 received no desipramine reducing striatal and hippocampal NE content 64% and 86% respectively. In experiment 1, the development and expression of L-DOPA-induced abnormal involuntary movements (AIMs) and rotations were examined. L-DOPA efficacy using the forepaw adjusting steps (FAS) test was also assessed in DA- and DA+NE-lesioned rats. In experiment 2, DA- and DA+NE-lesioned rats received pre-treatments of idazoxan or propranolol followed by L-DOPA after which the effects of these adrenergic compounds were observed. Results demonstrated that moderate NE loss reduced the development and expression of AIMs and rotations but not L-DOPA efficacy while anti-dyskinetic efficacy of α2- and β-adrenergic receptor blockade was maintained. These findings suggest that the NE system modulates LID and support the continued investigation of adrenergic compounds for the improved treatment of PD.
authors: Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY 13902, USA.
authors: Christopher J
authors: CJ
authors: Barnum
authors: Nirmal
authors: N
authors: Bhide
authors: David
authors: D
authors: Lindenbach
authors: Margaret A
authors: MA
authors: Surrena
authors: Adam A
authors: AA
authors: Goldenberg
authors: Stefanie
authors: S
authors: Tignor
authors: Anna
authors: A
authors: Klioueva
authors: Hannah
authors: H
authors: Walters
authors: Christopher
authors: C
authors: Bishop
mesh_terms: D059331:Adrenergic Neurons / Q000187:drug effects*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D019329:Idazoxan / Q000627:therapeutic use; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013563:Sympathectomy, Chemical
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018696:Neuroprotective Agents; D007980:Levodopa; D016627:Oxidopamine; D011433:Propranolol; D003891:Desipramine; D019329:Idazoxan