title: Behavioral and neurochemical effects of chronic L-DOPA treatment on nonmotor sequelae in the hemiparkinsonian rat.
abstract: Depression and anxiety are the prevalent nonmotor symptoms that worsen quality of life for Parkinson's disease (PD) patients. Although dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. To delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-hydroxydopamine or sham lesions and were treated daily with L-DOPA (12 mg/kg+benserazide, 15 mg/kg, subcutaneously) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One hour after the final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed through high-performance liquid chromatography for monoamine levels. In locomotor chambers and social interaction, DA lesions exerted mild anxiogenic effects. Surprisingly, chronic L-DOPA treatment did not improve these effects. Although DA lesion reduced climbing behaviors on day 2 of exposure to the forced swim test, chronic L-DOPA treatment did not reverse these effects. Neurochemically, L-DOPA treatment in hemiparkinsonian rats reduced norepinephrine levels in the prefrontal cortex, striatum, and hippocampus. Collectively, these data suggest that chronic L-DOPA therapy in severely DA-lesioned rats does not improve nonmotor symptoms and may impair nondopaminergic processes, indicating that long-term L-DOPA therapy does not exert necessary neuroplastic changes for improving affect.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, New York, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Eskow Jaunarajs
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Dupre
authors.forename: Corinne Y
authors.initials: CY
authors.lastname: Ostock
authors.forename: Thomas
authors.initials: T
authors.lastname: Button
authors.forename: Terrence
authors.initials: T
authors.lastname: Deak
authors.forename: Christopher
authors.initials: C
authors.lastname: Bishop
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D035841:Behavioral Research; D015306:Biogenic Monoamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D003863:Depression / Q000188:drug therapy; D004298:Dopamine / Q000031:analogs & derivatives / Q000502:physiology; D015259:Dopamine Agents / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015306:Biogenic Monoamines; D015259:Dopamine Agents; D007980:Levodopa; D016627:Oxidopamine; D004298:Dopamine