Data for this review were identified by searches of MEDLINE, Psychlnfo, PubMed, and Web of Science databases, together with references from relevant articles. We used the search terms “abuse”, “addiction”, “agonist”, “apomorphine”, “approach”, “bromocriptine”, “cabergoline”, “dependence”, “dopamine”, “dyskinesias”, “euphoria”, “habit”, “hedonic”, “hoarding”, “levodopa”, “mood”, “nucleus accumbens”, “Parkinson's”, “pergolide”, “place preference”, “pleasure”, “pramipexole”, “psychiatric”,
ReviewCompulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry?
Section snippets
Is this syndrome a substance dependence disorder or an addiction?
It can be difficult to diagnose a DSM-IV “substance dependence disorder”44 in a patient with a progressive incurable neurological disease. Development of tolerance is difficult to detect when a symptomatic treatment relieves the incapacitating physical symptoms. DRT requirements increase as motor disability progresses. Pharmacological tolerance to the motor effects of DRT has been described, but is not a major management problem.45, 46 Patients also experience adverse effects if withdrawn from
Do models of psychostimulant addiction help to understand compulsive DRT use in PD?
Current theories of addiction incorporate the idea that drugs activate and, via neuroadaptive processes, change dopaminergic neurotransmission in the nucleus accumbens and related circuitry, altering important reward-related processes (although different theories posit different processes).49
Implications for management
Ideally, the risk of developing compulsive DRT use should be minimised, because once patients have developed the disorder, long term management becomes difficult. Differences between patients, and pharmacological and environmental factors should be taken into account when using DRT to treat patients with PD. The potential influence of factors that might lead to an increased susceptibility to both locomotor and incentive sensitisation can be minimised by accounting for sex-related,
Summary and conclusions
Compulsive use of DRT by patients with PD, although rare, is of both clinical and theoretical importance. The major theories of psychostimulant addiction may help explain some of the phenomena seen in the dopamine dysregulation syndrome. All of the major theories can partly explain the syndrome, but it is unlikely that any one theory can explain all the features. The theories are not necessarily mutually exclusive, and dopamine dysregulation syndrome may not represent a unitary phenomenon with
Search strategy and selection criteria
References (131)
- et al.
Dopamine systems in the primate brain
- et al.
Clinical effects of amphetamine and L-DOPA on sexuality and aggression
Comp Psychiat
(1976) - et al.
Levodopa dependence and hypersexuality in an older Parkinson's disease patient
Am J Geriat Psychiat
(1995) Punding on levodopa
Biol Psychiatry
(1994)- et al.
A “crash” course on psychostimulant withdrawal as a model of depression
Trends Pharmacol Sci
(2002) - et al.
Conditioned place preference induced by a combination of L-Dopa and a COMT inhibitor, entacapone, in rats
Pharm Biochem Behav
(1998) Different effects of short- and long-term treatment with imipramine on the apomorphineand food-induced place preference conditioning in rats
Pharmacol Biochem Behav
(1988)- et al.
The dopamine D2 receptor agonists, quinpirole and bromocriptine produce conditioned place preferences
Prog Neuropsychopharmal Biol Psychiatr
(1988) - et al.
Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens
Pharmacol Biochem Behav
(1985) - et al.
Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men
Neuropsychopharm
(2002)