Highly-selective µ-opioid receptor antagonism does not block L-DOPA-induced dyskinesia in a rodent model.

TitleHighly-selective µ-opioid receptor antagonism does not block L-DOPA-induced dyskinesia in a rodent model.
Publication TypeJournal Article
Year of Publication2020
AuthorsBartlett MJ, So LY, Szabò L, Skinner DP, Parent KL, Heien ML, Vanderah TW, Polt R, Sherman SJ, Falk T
JournalBMC Res Notes
Date Published2020 Mar 12
KeywordsAnimals, Disease Models, Animal, Dyskinesia, Drug-Induced, Glycopeptides, Levodopa, Male, Morphine, Narcotic Antagonists, Nociception, Rats, Sprague-Dawley, Receptors, Opioid, mu

OBJECTIVES: Dopamine-replacement utilizing L-DOPA is still the mainstay treatment for Parkinson's disease (PD), but often leads to development of L-DOPA-induced dyskinesia (LID), which can be as debilitating as the motor deficits. There is currently no satisfactory pharmacological adjunct therapy. The endogenous opioid peptides enkephalin and dynorphin are important co-transmitters in the direct and indirect striatofugal pathways and have been implicated in genesis and expression of LID. Opioid receptor antagonists and agonists with different selectivity profiles have been investigated for anti-dyskinetic potential in preclinical models. In this study we investigated effects of the highly-selective μ-opioid receptor antagonist CTAP (> 1200-fold selectivity for μ- over δ-opioid receptors) and a novel glycopeptide congener (gCTAP5) that was glycosylated to increase stability, in the standard rat LID model.

RESULTS: Intraperitoneal administration (i.p.) of either 0.5 mg/kg or 1 mg/kg CTAP and gCTAP5 completely blocked morphine's antinociceptive effect (10 mg/kg; i.p.) in the warm water tail-flick test, showing in vivo activity in rats after systemic injection. Neither treatment with CTAP (10 mg/kg; i.p.), nor gCTAP5 (5 mg/kg; i.p.) had any effect on L-DOPA-induced limb, axial, orolingual, or locomotor abnormal involuntary movements. The data indicate that highly-selective μ-opioid receptor antagonism alone might not be sufficient to be anti-dyskinetic.

Alternate JournalBMC Res Notes
PubMed ID32164786
PubMed Central IDPMC7066739
Faculty Member Reference: 
Torsten Falk, Ph.D.
Robin Polt, Ph.D.
Todd Vanderah, PhD