title: The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.
abstract: In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.
authors: Department of Psychiatry, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
authors: Rosa L
authors: RL
authors: Drijgers
authors: Frans R J
authors: FR
authors: Verhey
authors: Gerrit
authors: G
authors: Tissingh
authors: Peter H M F
authors: PH
authors: van Domburg
authors: Pauline
authors: P
authors: Aalten
authors: Albert F G
authors: AF
authors: Leentjens
mesh_terms: D000339:Affect / Q000187:drug effects / Q000502:physiology*; D000368:Aged; D052160:Benzothiazoles / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000523:psychology*; D000077487:Pramipexole; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D000077487:Pramipexole