{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:02:02Z","timestamp":1781974922665,"version":"3.54.5"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Nicotine induces kinetic tremor, which resembles pharmacological features of essential tremors, via activating the inferior olive (IO) neurons. Since nicotine is known to enhance dopamine release by stimulating \u03b14\u03b22 and\/or \u03b16 nACh receptors, we examined the effects of various dopamine receptor ligands on nicotine-induced tremor to clarify the role of the dopaminergic system in modulating nicotine tremor. A tremorgenic dose of nicotine increased the dopamine level in the pons and medulla oblongata (P\/MO), and the levels of dopamine metabolites in the hippocampus, P\/MO, and striatum. Treatment of animals with the D<jats:sub>1\/5<\/jats:sub> agonist SKF-38393 inhibited the induction of nicotine tremor, whereas the D<jats:sub>3<\/jats:sub> agonist PD-128,907 facilitated nicotine-induced tremor. The D<jats:sub>2<\/jats:sub> agonist sumanirole showed no effect. In addition, nicotine tremor was significantly enhanced by the D<jats:sub>1\/5<\/jats:sub> antagonist SCH-23390 and inhibited by the D<jats:sub>3<\/jats:sub> antagonist U-99194. Neither the D<jats:sub>2<\/jats:sub> (L-741,626) nor D<jats:sub>4<\/jats:sub> (L-745,870) antagonist affected the generation of nicotine tremor. Furthermore, microinjection of U-99194 into the cerebellum significantly inhibited nicotine-induced tremor, whereas its injection into IO or the striatum did not affect tremor generation. Although intrastriatal injection of SCH-23390 showed no effects, its injection into IO tended to enhance nicotine-induced tremor. The present study suggests that dopamine D<jats:sub>3<\/jats:sub> and D<jats:sub>1\/5<\/jats:sub> receptors regulate the induction of nicotine tremor in an opposite way, D<jats:sub>3<\/jats:sub> receptors facilitately and D<jats:sub>1\/5<\/jats:sub> receptors inhibitorily. In addition, the cerebellar D<jats:sub>3<\/jats:sub> receptors may play an important role in modulating the induction of nicotine tremor mediated by the olivo-cerebellar system.<\/jats:p>","DOI":"10.3389\/fphar.2022.938175","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T05:56:40Z","timestamp":1655359000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor"],"prefix":"10.3389","volume":"13","author":[{"given":"Masaki","family":"Kato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naofumi","family":"Kunisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Higor A.","family":"Iha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.pnpbp.2005.04.020","article-title":"Dopamine D3 Modulation of Locomotor Activity and Sleep in the Nucleus Accumbens and in Lobules 9 and 10 of the Cerebellum in the Rat","volume":"29","author":"Barik","year":"2005","journal-title":"Prog. 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