Dataset Information

Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

ABSTRACT:

Objective

Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).

Methods

Following overnight withdrawal of antiparkinsonian medication, patients were studied with H?(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.

Results

We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.

Conclusions

We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.

SUBMITTER: van Eimeren T

PROVIDER: S-EPMC3033606 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

van Eimeren T T Pellecchia G G Cilia R R Ballanger B B Steeves T D L TD Houle S S Miyasaki J M JM Zurowski M M Lang A E AE Strafella A P AP

Neurology 20101006 19

<h4>Objective</h4>Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a ...[more]

PMID: 20926784

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Project description:Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence.Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence.Computer-assisted telephone interviews in the community.Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry.Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule.All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA ?=?0.22; 95% confidence interval (CI)?=?0.10-0.34] and non-shared environmental components (environmental correlation rE ?=?0.24; 95% CI?=?0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA ?=?0.32; 95% CI?=?0.05-1.0; rE ?=?0.36; 95% CI?=?0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA ?=?0.58; 95% CI?=?0.45-0.73).Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions (perhaps relating to availability and legality) may help to diminish the relationship between problem/pathological gambling and tobacco- and cannabis-use disorders.

Dataset Information

Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

Objective

Methods

Results

Conclusions

Publications

Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

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