Abstract
Continuous dopaminergic receptor stimulation is now considered as an interesting approach for the control of motor complications often seen in parkinsonian patients treated chronically with levodopa. Cabergoline, which is a long-acting dopamine D2-like receptor agonist, has been tried recently with good results as an adjunct in patients already on levodopa-therapy. Thus, the present study was designed to test the effects of repeated s.c administration of cabergoline as sole therapeutic agent during a month in 3 drug-naive MPTP parkinsonian monkeys to see whether or not cabergoline, given every other day at 0.25 mg/kg, would have a sustained antiparkinsonian effect and would induce dyskinesias. The animals were rated to quantify the antiparkinsonian as well as the dyskinetic response and gross locomotor activity was monitored by photocells. The averaged locomotor response, initially greatly increased (~9 times higher than after saline treatment in the same animals), decreased by ~50% after 2 weeks but was thereafter maintained at this level until the end of the study. The parkinsonian features were improved in a sustained manner in all monkeys and transient dyskinesias (week 1 and 2) were present in 2 of 3 monkeys. After sacrifice receptor binding assays were performed on striatal and pallidal tissues homogenates with tritiated selective ligands and compared with those of 3 normal and 3 MPTP-exposed monkeys otherwise untreated. A significant decrease in dopamine D2-like receptor density in the putamen (-36% on average vs. untreated MPTP-exposed monkeys) may be involved in the behavioral partial tolerance to antiparkinsonian effect of cabergoline and the disappearance of dyskinesias. A reversal of the supersensitivity of GABA(A) receptor in the internal segment of the globus pallidus (-15% on average vs. untreated MPTP-exposed monkeys) may also be implicated in this latter behavioral effect.
Original language | English |
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Pages (from-to) | 298-306 |
Number of pages | 9 |
Journal | Brain Research |
Volume | 735 |
Issue number | 2 |
DOIs | |
State | Published - Oct 7 1996 |
Bibliographical note
Funding Information:The authors wish to thank Ren6 Boucher, Laurent Gr6goire and Gaston C6t6 for their excellentt echnical assistanceT.h eyare also gratefutlo Adria Laboratoriefso r the generougs ift of cabergolineR.. G. holds a studentship grantf romthe FCAR-FRSQ-Sant6a nd M.G. from FRSS-ACIM/CRMC. This work was supportedb y the Medical ResearchC ounciland the ParkinsonF oundationo f Canada.
Keywords
- Cabergoline
- Dopamine D
- Dyskinesia
- GABA
- MPTP
- Parkinson's disease
- Receptor
- Receptor
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology