Iatrogenic gambling disorders in Parkinson’s disease

Parkinson’s Disease (PD) is a neurodegenerative disorder affecting about 1% of the population and is the second most common neurodegenerative disorder in individuals over the age of 55.  Tremor and rigidity are the hallmark of the disease, but cognitive symptoms may also appear as the severity of the disease increases.  Unfortunately, the more traditional drug treatment for PD, L-DOPA, has shown over time to produce debilitating side-effects like dyskinesia.  For this reason, physicians increasingly prescribed selective dopamine D2/3 receptor agonists, such as pramipexole and ropinirole to treat the motor symptoms of PD.  However, instances of serious impulse control disorders (ICD), including pathological gambling (PG) have been described in some patients (~16%) as a result of treatment with this newer type of medications.  Our lab has demonstrated that rats, just like humans, can gamble for rewards on the Betting task, a gambling paradigm which captures irrational decision-making under uncertainty in which rats choose between a guaranteed reward versus a 50:50 chance of double that reward or nothing.  This task allows us to investigate the effect of chronic administration of the D2/3 dopamine agonist drug ropinirole on gambling behaviours using a subcutaneous osmotic pump in healthy rats and in a 6-hydroxydopamine (6-OHDA) lesion model of PD.  The animal model of PD and the betting task helps us elucidate the mechanism underlying drug-induced development of ICDs such as gambling and characterize any changes in dopamine receptor expression and related intracellular signaling pathways in striatal regions that accompany the behavioural manifestations.