The
opioid peptides localized in striatal projection neurons are of great relevance to
Parkinson's disease, not only as a consequence of their distribution, but also due to the pronounced changes in expression seen in
Parkinson's disease. It has long been suspected that increased expression of
enkephalin may represent one of the many mechanisms that compensate for
dopamine (DA) depletion in
Parkinson's disease. Here we demonstrate that a systemically delivered, selective delta
opioid agonist (
SNC80) has potent antiparkinsonian actions in both rat and primate models of
Parkinson's disease. In rats treated with either the D2-preferring DA antagonist
haloperidol (1 mg/kg) or the selective D1 antagonist
SCH23390 (1 mg/kg), but not a combination of D1 and D2 antagonists,
SNC80 (10 mg/kg) completely reversed the
catalepsy induced by DA antagonists. In rats rendered immobile by treatment with
reserpine,
SNC80 dose-dependently reversed akinesia (EC(50) 7.49 mg/kg). These effects were dose-dependently inhibited (IC(50) 1.05 mg/kg) by a selective delta
opioid antagonist (
naltrindole) and by
SCH23390 (1 mg/kg), but not by
haloperidol (1 mg/kg).
SNC80 also reversed parkinsonian symptoms in the
MPTP-treated marmoset.
At 10 mg/kg (ip), scores measuring
bradykinesia and posture were significantly reduced and motor activity increased to levels comparable with pre-
MPTP-treatment scores. Any treatment that serves to increase
delta opioid receptor activation may be a useful therapeutic strategy for the treatment of
Parkinson's disease, either in the early stages or as an adjunct to
dopamine replacement
therapy. Furthermore, enhanced
enkephalin expression observed in
Parkinson's disease may serve to potentiate
dopamine acting preferentially at D1 receptors.