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Hyperactivity of excitotoxic cerebellar climbing fibres may underlie essential tremor and has been induced in rodents by systemic harmaline administration. Cannabinoid (CB) receptor agonists can cause motor disturbances; although, there are also anecdotal reports of therapeutic benefits of cannabis in motor disorders. We set out to establish the effects of CB receptor agonism and antagonism on an established rodent model of ET using a battery of accepted behaviour assays in order to determine the risk and therapeutic potential of modulating the endocannabinoid system in ET.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Behavioural effects of systemic treatment with a CB receptor agonist (0.1, 0.5 and 1\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>WIN55, 212\u20132) or two CB<jats:sub>1<\/jats:sub>receptor antagonists (1\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0AM251 and 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>rimonabant) on tremor induced in rats by harmaline (30\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>; i.p.), were assessed using tremor scoring, open field, rotarod, grip and gait tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Overall, harmaline induced robust tremor that was typically worsened across the measured behavioural domains by CB receptor agonism but ameliorated by CB<jats:sub>1<\/jats:sub>receptor antagonism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results provide the first evidence of the effects of modulating the endocannabinoid system on motor function in the harmaline model of ET. Our data suggest that CB<jats:sub>1<\/jats:sub>receptor manipulation warrants clinical investigation as a therapeutic approach to protection against behavioural disturbances associated with ET.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13581","type":"journal-article","created":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:12:48Z","timestamp":1471824768000},"page":"3196-3207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cannabinoid type 1 receptor antagonism ameliorates harmaline\u2010induced essential tremor in rat"],"prefix":"10.1111","volume":"173","author":[{"given":"Hassan","family":"Abbassian","sequence":"first","affiliation":[{"name":"Neuroscience Research Center, Neuropharmacology Institute Kerman University of Medical Sciences Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Whalley","sequence":"additional","affiliation":[{"name":"Department of 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