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The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats.
Brain Res 2010; 1363:40-8BR

Abstract

The long-term use of levodopa as a pharmacotherapy for Parkinson's disease is limited by the development of levodopa-induced dyskinesias. However, recent studies have suggested that pharmacological targeting of the endocannabinoid system may provide a viable adjunct to suppress these motor side effects. Thus, this study sought to determine the effect of pharmacologically activating or blocking endocannabinoid signalling on levodopa-induced dyskinesias in a rat model. Male Sprague-Dawley rats with 6-hydroxydopamine lesions were made dyskinetic by 6 weeks of daily levodopa injections (10mg/kg s.c.). Rats that developed stable abnormal involuntary movements (AIMs) received acute injections of the cannabinoid receptor agonist, HU210 (0.0, 0.5, 5.0, and 50.0 μg/kg i.p.), or the CB(1) receptor antagonist/inverse agonist, AM251 (0.0 and 3.0mg/kg i.p.), whereas rats that did not develop stable AIMs received injections of the CB(1) receptor antagonist/inverse agonist, rimonabant (0.0 and 3.0mg/kg i.p.), for 18 days. In the dyskinetic rats, the highest dose of HU210 significantly reduced certain subtypes of AIMs but it also impaired normal motor functioning, while AM251 had no effect on AIMs. In the non-dyskinetic rats, rimonabant precipitated certain subtypes of AIMs. Overall, this study demonstrates that the anti-dyskinetic effects of cannabinoid receptor agonists may not be dissociable from their motor suppressant effects thereby limiting their potential usefulness for treating established dyskinesias in parkinsonism. However, it is intriguing that blockade of endocannabinoid-CB(1) signalling can unmask levodopa-induced AIMs, and this finding suggests that endocannabinoid tone may confer protection against the development of levodopa-induced dyskinesias.

Authors+Show Affiliations

Department of Pharmacology & Therapeutics, National University of Ireland, Galway, Ireland. s.walsh12@nuigalway.ieNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20888328

Citation

Walsh, Sinéad, et al. "The Effects of Cannabinoid Drugs On Abnormal Involuntary Movements in Dyskinetic and Non-dyskinetic 6-hydroxydopamine Lesioned Rats." Brain Research, vol. 1363, 2010, pp. 40-8.
Walsh S, Gorman AM, Finn DP, et al. The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats. Brain Res. 2010;1363:40-8.
Walsh, S., Gorman, A. M., Finn, D. P., & Dowd, E. (2010). The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats. Brain Research, 1363, pp. 40-8. doi:10.1016/j.brainres.2010.09.086.
Walsh S, et al. The Effects of Cannabinoid Drugs On Abnormal Involuntary Movements in Dyskinetic and Non-dyskinetic 6-hydroxydopamine Lesioned Rats. Brain Res. 2010 Dec 2;1363:40-8. PubMed PMID: 20888328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats. AU - Walsh,Sinéad, AU - Gorman,Adrienne M, AU - Finn,David P, AU - Dowd,Eilís, Y1 - 2010/10/01/ PY - 2010/08/06/received PY - 2010/09/22/revised PY - 2010/09/24/accepted PY - 2010/10/5/entrez PY - 2010/10/5/pubmed PY - 2011/2/25/medline SP - 40 EP - 8 JF - Brain research JO - Brain Res. VL - 1363 N2 - The long-term use of levodopa as a pharmacotherapy for Parkinson's disease is limited by the development of levodopa-induced dyskinesias. However, recent studies have suggested that pharmacological targeting of the endocannabinoid system may provide a viable adjunct to suppress these motor side effects. Thus, this study sought to determine the effect of pharmacologically activating or blocking endocannabinoid signalling on levodopa-induced dyskinesias in a rat model. Male Sprague-Dawley rats with 6-hydroxydopamine lesions were made dyskinetic by 6 weeks of daily levodopa injections (10mg/kg s.c.). Rats that developed stable abnormal involuntary movements (AIMs) received acute injections of the cannabinoid receptor agonist, HU210 (0.0, 0.5, 5.0, and 50.0 μg/kg i.p.), or the CB(1) receptor antagonist/inverse agonist, AM251 (0.0 and 3.0mg/kg i.p.), whereas rats that did not develop stable AIMs received injections of the CB(1) receptor antagonist/inverse agonist, rimonabant (0.0 and 3.0mg/kg i.p.), for 18 days. In the dyskinetic rats, the highest dose of HU210 significantly reduced certain subtypes of AIMs but it also impaired normal motor functioning, while AM251 had no effect on AIMs. In the non-dyskinetic rats, rimonabant precipitated certain subtypes of AIMs. Overall, this study demonstrates that the anti-dyskinetic effects of cannabinoid receptor agonists may not be dissociable from their motor suppressant effects thereby limiting their potential usefulness for treating established dyskinesias in parkinsonism. However, it is intriguing that blockade of endocannabinoid-CB(1) signalling can unmask levodopa-induced AIMs, and this finding suggests that endocannabinoid tone may confer protection against the development of levodopa-induced dyskinesias. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/20888328/abstract/The_effects_of_cannabinoid_dr L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(10)02152-9 DB - PRIME DP - Unbound Medicine ER -