Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders.
Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.
Voon
Valerie
V
Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK. voonval@gmail.com
Fernagut
Pierre-Olivier
PO
Wickens
Jeff
J
Baunez
Christelle
C
Rodriguez
Manuel
M
Pavon
Nancy
N
Juncos
Jorge L
JL
Obeso
José A
JA
Bezard
Erwan
E
D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001332:Automatism / Q000503:physiopathology; D003192:Compulsive Behavior / Q000139:chemically induced / Q000523:psychology; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005715:Gambling / Q000523:psychology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D011605:Psychoses, Substance-Induced / Q000523:psychology; D012725:Sexual Behavior
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine