Neural reward processing under dopamine agonists: Imaging

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Abstract

Impulse control disorders (ICDs) are increasingly reported as a considerable side-effect of treatment with dopaminergic medication (both levodopa and dopamine agonists (DA)). ICDs together with punding are described within the entity of dopamine dysregulation syndrome along with immediate reward seeking and addictive behaviors. The brain functions involved in reward processing in general and their modulation by medication can be characterized by neuropsychological assessments and underlying neurobiology can be investigated by functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). By this approach, functional changes of brain areas involved in reward processing under short-term or chronic DA therapy were studied. Functional changes in a network involving striatal–thalamic loops, key structures of the reward system, together with limbic areas (such as the amygdala) and the ventral tegmental area could be related to pharmacological alterations of reward processing by dopaminergic medication. In particular, altered ventral striatal functioning seems to relate to ICDs such as pathological gambling. A general medication effect in patients under DA in terms of a sensitization toward ICD could be demonstrated. A synopsis is given on the applications of functional neuroimaging to investigate reward processing and the influence of dopaminergic medication.

Introduction

The dopaminergic reward system has been implicated to be involved in the modulation of impulsive behaviors, and the appearance of ICD is seen as the result of a dopaminergic dysregulation because of both extrinsic as well as intrinsic factors [1]. In Parkinson's disease (PD), intrinsic factors such as dopamine deficiency play a substantial role in PD-associated neuropsychiatric disturbances; nevertheless ICD are an increasingly recognized side-effect of treatment with dopaminergic medication (both levodopa and DA) as external trigger of dopamine dysregulation. Also in patients with dopaminergic medication for restless legs syndrome (RLS), a sensitization toward impulse control disorders under DA therapy has been reported. As underlying pathomechanism of medication triggered dopaminergic dysregulation, a progressive neuroadaptation in dopamine projections to the nucleus accumbens-related circuitry has been suggested [2]. Progressive neuroadaption results in sensitization that causes a progressive increase in the rewarding effect of dopaminergic drugs with repeated use [3].

Impulsive–compulsive disorders (ICD) are characterized by neuropsychiatric symptoms with an inability to resist an impulse, drive or temptation to perform an act that is harmful to the person itself or others [3]. These behaviors are performed repetitively, excessively or compulsively and thus interfere in major areas of life functioning [1]. A considerable variety in the clinical expression of symptoms can be recognized in PD patients [4]. The spectrum of ICD comprises the dopamine deficiency syndrome (DDS-1) with immediate reward seeking behavior, the dopamine dependency syndrome (DDS-2) with addictive behavior as well as the dopamine dysregulation syndrome (DDS-3) with both addictive and stereotyped behavior and impulse-control disorders (ICD) such as pathological gambling, binge eating or compulsive shopping [1]. The lifetime prevalence of ICD related to dopaminergic drugs in PD patients is reported to be 6–9% increasing to 14% with dopamine-replacement therapy such as dopamine agonists (DA) [3], [5], [6]. Hence, DA treatment in PD has been associated with 2- to 3.5-fold increased odds of developing ICD [5].

Section snippets

Reviewers' search strategy and selection criteria

References for this review were identified through searches of PubMed by conducting a Boolean search strategy. The search keywords were impulsive–compulsive disorders, impulse control disorders, dopamine dysregulation syndrome, dopaminergic reward system, Parkinson's disease, dopamine agonists, levodopa, imaging, magnetic resonance imaging, and positron emission tomography. Only papers in anglophone peer reviewed journals were regarded for this review. Out of the publications identified by this

Neurobiological correlates of pathological reward processing

As potential neuropathological correlates of DDS and ICD, altered information downstream from the ventral striatum to dorsal striatal structures has been suggested. The ventral striatum is closely connected with limbic structures including the amygdala, the hippocampal formation, and the anterior cingulate cortex. Attenuated or augmented dopaminergic input to the ventral striatum may lead to a deficient activation of ventral striatal areas and dysregulated further downstream to the dorsal motor

Neuroimaging correlates of reward processing and its changes under dopaminergic drugs

Altered reward processing under dopaminergic medication with levodopa or dopamine agonists was studied in healthy subjects in order to depict ‘pure’ pharmacological effects as well as in patients with Parkinson's disease or Restless Legs Syndrome to enlarge the (clinical) understanding of the dopaminergic effects in diseased brains (Fig. 1).

While recent studies almost exclusively made use of fMRI, earlier investigations also applied positron emission tomography (PET). Using PET and 11

Summary

In summary, as supported by the above-named key studies, functional neuroimaging, i.e. mainly fMRI, has proven to be a powerful technique in the study of the dopaminergic reward system as involved in the development of ICD and DDS and its alterations under dopaminergic drugs. Neuroimaging has contributed substantially to further our understanding of the function of numerous reward-related cerebral networks, and allowed examining how reward-related information is implicated in decision making

Conflict of interest statement

None.

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