The opioid agonist morphine decreases the dyskinetic response to dopaminergic agents in parkinsonian monkeys.

In parkinsonian patients as well as in primate models with levodopa-induced dyskinesias (LID), an increase in the expression of preproenkephalin in the striatal output pathways has been demonstrated. Does this increase contribute to the development of LID, or does it rather act as a protection mechanism? To clarify this question, we have investigated the effect of different doses of morphine on the dyskinetic response to L-DOPA, a D2 agonist, and a D1 agonist. We have used MPTP-treated cynomolgus monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L-DOPA. Co-administration of morphine with dopaminergic agents produces a significant reduction in the severity of dyskinesias, while it does not affect the anti-parkinsonian efficacy of the treatment. This study suggests that the increased production of opioids in the striatal projection neurons might have a protective role to compensate the changes in synaptic transmissions that are responsible for dyskinesias, rather than be the cause of dyskinesias.