Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease

Lemke, Matthias R.; Brecht, H. M.; Koester, J.; Reichmann, Heinz

doi:10.1016/j.jns.2006.05.024

Cited by 120 publications

(71 citation statements)

References 28 publications

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“…A titration approach would not only minimize drug-related adverse effects but also allow to test the hypothesis that higher doses of pramipexole would increase, rather than decrease, reward responsiveness due to a preferential post-synaptic DA action. This speculation is consistent with (1) findings in rodents showing that pramipexole is effective in reversing anhedonia produced by the chronic mild stress paradigm (Willner et al 1994) and has antidepressant properties (Maj and Rogoz 1999;(Lehr 2002); and (2) clinical findings showing that higher doses of pramipexole ameliorate depressive symptoms in PD patients (Lemke et al 2006) and treatment-resistant depression (Corrigan et al 2000;Cassano et al 2004). Collectively, these preclinical and clinical findings raise the possibility that sustained pramipexole administration may alleviate depressive-particularly anhedonic-symptoms through its action on D3 receptors concentrated in the nucleus accumbens.…”

Section: Discussionsupporting

confidence: 87%

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

et al. 2007

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Rationale-The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans.Objectives-To evaluate the effect of a single, low dose of a D2/D3 agonist-pramipexole-on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms.Methods-Using a double-blind design, a single 0.5 mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks.Results-As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared.Conclusions-These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed.

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Section: Discussionsupporting

confidence: 87%

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

et al. 2007

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“…It is possible that the UPDRS does not completely capture all features related to parkinsonian disability, especially in early patients. In this regard, it is noteworthy that the dopamine agonist pramipexole has been shown to have antidepressant effects in double-blind, controlled studies, [337][338][339] and quality of life scores at 4 years in the CALM-PD study were comparable in the two groups, trending in favor of pramipexole therapy. 336 It has been suggested that the UPDRS scale is not particularly sensitive to changes that occur in patients with early PD.…”

Section: Time (Months)mentioning

confidence: 94%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

760

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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“…In this line, the dopamine agonist pergolide improved depressed patients in an open, non-blind trial (Izumi et al 2000). In addition, pramipexole, a D 2 /D 3 receptor agonist, has been proven to be as effective as fluoxetine, a selective serotonin reuptake inhibitor (SSRI), in treating patients with severe depressive symptoms (Corrigan et al 2000 ;Shannon et al 1997) and to reduce the frequency of depression and anhedonia in PD patients with depression (Lemke et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Locus coeruleus and dorsal raphe neuron activity and response to acute antidepressant administration in a rat model of Parkinson's disease

Miguélez

Grandoso

Ugedo

2010

Int. J. Neuropsychopharm.

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In addition to noradrenergic and serotonergic systems, dopaminergic neurotransmission seems to play an important role in the aetiopathogenesis of, and recovery from, depression. Moreover, the incidence of depression is higher in patients affected by diseases where the dopaminergic system is highly impaired, such us Parkinson's disease. Here, we investigated the effects of dopamine degeneration on the activity and response to antidepressants of locus coeruleus (LC) noradrenergic and dorsal raphe nucleus (DRN) serotonergic neurons. To this end, single-unit extracellular recordings were performed in control and 6-hydroxydopamine (6-OHDA)-lesioned animals. In this latter group, LC neurons showed a lower basal firing rate as well as less sensitivity to the administration of the serotonin reuptake inhibitor, fluoxetine. The rest of electrophysiological parameters and the response to the administration of the a 2 -adrenoceptor agonist, clonidine and the noradrenaline reuptake inhibitor, reboxetine remained unaltered. In the DRN, dopamine depletion did not modify the basal electrophysiological characteristics and the response to clonidine or fluoxetine administration. In contrast, the administration of reboxetine more efficiently induced an inhibitory effect in the lesioned group. In additional analyses it was observed that while in control animals, LC and DRN basal firing rate was significantly correlated, this relationship was lost after the 6-OHDA lesion. In conclusion, dopaminergic degeneration alters LC neuron basal activity, the relationship/syntony between both nuclei, and their response to antidepressants. These findings shed fresh light on our understanding of the role of dopamine in depression and the mechanism action of antidepressants.

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Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease

Cited by 120 publications

References 28 publications

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Locus coeruleus and dorsal raphe neuron activity and response to acute antidepressant administration in a rat model of Parkinson's disease

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