Long-lasting effects of ceruletide on L-Dopa-induced dyskinesias in monkey

Abstract

The long-lasting effects of ceruletide (CLT), a cholecystokinin-8 (CCK-8) analogue, on involuntary movements were investigated. Nine monkeys were used. One group (6 monkeys) received unilateral lesions to the ventromedial tegmentum (VMT) of the midbrain. The second group (3 monkeys) served as controls.
Hypokinesia was produced after lesioning of the VMT. Administration of a large amount of L-Dopa or direct intracaudate injection of dopamine (DA) relieved the symptoms initially but then induced dyskinesias later. Two monkeys with reproducible dyskinesias were chosen for further study.
Systemically administered CLT combined with L-Dopa improved the hypokinesia without inducing dyskinesia. These effects of a single dose of 50 μg/kg CLT continued up to 9 days. Direct combined administration of CLT and DA into the dorsomedial part of the head of the caudate nucleus ipsilateral to the VMT lesion improved the hypokinesia without inducing dyskinesia. The effects of a single direct injection of 20 ng/kg CLT persisted for 3 days.
The long-lasting effects of systemically and directly administered CLT were confirmed. These findings suggest that CLT modulates the DA system indirectly through the central CCK system, especially in the dorsomedial part of the head of the caudate nucleus.