April 2011
O'Sullivan SS, Wu K, Politis M, Lawrence AD, Evans AH, Bose SK, Djamshidian A, Lees AJ, Piccini P
Impulsive-compulsive behaviours are a significant source of morbidity
for patients with Parkinson’s disease receiving dopaminergic
therapy. The development of these behaviours may
reflect sensitization of the neural response to non-drug rewards,
similar
to that proposed for sensitization to drug rewards
in addiction. Here, by using 11C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and l-dopa
challenge in patients with Parkinson’s disease with and without
impulsive-compulsive behaviours on striatal levels of
synaptic dopamine.
Eighteen patients (11 with and
seven without impulsive-compulsive behaviours) underwent three 11C-raclopride
positron emission tomography scans. The impulsive-compulsive behaviours
included hypersexuality, binge eating,
punding, compulsive use of dopamine replacement
therapy, compulsive buying and pathological gambling, with eight
patients
exhibiting more than one impulsive-compulsive
behaviour. There were no significant differences in baseline dopamine D2
receptor
availability between the Parkinson’s disease
groups. No differences were found when comparing the percentage change
of raclopride
binding potential between the two Parkinson’s
disease groups following l-dopa challenge with
neutral cues. The group with Parkinson’s disease with
impulsive-compulsive behaviours had a greater reduction
of ventral striatum 11C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following l-dopa challenge (16.3% compared with 5.8% in Parkinson’s disease controls, P
= 0.016).
The heightened response of striatal reward circuitry to
heterogeneous reward-related visual cues among a group
of patients with different impulsive-compulsive
behaviours is consistent with a global sensitization to appetitive
behaviours
with dopaminergic therapy in vulnerable
individuals. Our findings are relevant for the broader debate on the
relation between
impulsive-compulsive behaviours and addictions and
may have important implications with regards to advertisement
legislation
in an effort to prevent the onset of behavioural
addictions.
