{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:10:23Z","timestamp":1781154623995,"version":"3.54.1"},"reference-count":62,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Tetrabenazine (TBZ), used for treating hyperkinetic disorders, inhibits vesicular monoamine transporter\u20102 (VMAT\u20102), which sequesters monoamines into vesicles for exocytosis. However, our knowledge of the effect of TBZ on monoaminergic transmission is limited. Herein, we provide neurochemical evidence regarding the effect of VMAT\u20102 inhibition on vesicular neurotransmitter release from the prefrontal cortex (PFC) and striatum (STR) (brain regions involved in characteristic TBZ treatment side effects). The interaction between TBZ and MDMA was also assessed regarding motor behaviour in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Vesicular storage capacity and release of [<jats:sup>3<\/jats:sup>H]\u2010noradrenaline ([<jats:sup>3<\/jats:sup>H]\u2010NA), [<jats:sup>3<\/jats:sup>H]\u2010dopamine ([<jats:sup>3<\/jats:sup>H]\u2010DA), [<jats:sup>3<\/jats:sup>H]\u2010serotonin ([<jats:sup>3<\/jats:sup>H]\u20105\u2010HT), and [<jats:sup>3<\/jats:sup>H]\u2010acetylcholine ([<jats:sup>3<\/jats:sup>H]\u2010ACh) was studied in mouse PFC and STR ex vivo slice preparations using electrical field stimulation. Additionally, locomotor activity was assessed in vehicle\u2010treated mice and compared with that of MDMA, TBZ, and co\u2010administered animals (n\u2009=\u20096) using the LABORAS system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>TBZ lowered the storage capacity and inhibited the vesicular release of [<jats:sup>3<\/jats:sup>H]\u2010NA and [<jats:sup>3<\/jats:sup>H]\u2010DA from the PFC, and [<jats:sup>3<\/jats:sup>H]\u2010DA and [<jats:sup>3<\/jats:sup>H]\u20105\u2010HT from the STR in a concentration\u2010dependent manner. Unlike vesamicol (vesicular ACh uptake inhibitor), TBZ failed to inhibit the vesicular release of [<jats:sup>3<\/jats:sup>H]\u2010ACh from the PFC. When the vesicular storage of the investigated monoamines was inhibited by TBZ in the PFC and STR, MDMA induced the release of transmitters through transporter reversal; MDMA dose dependently increased locomotor activity in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Our observations provide neurochemical evidence explaining the mechanism of VMAT\u20102 inhibitors in the brain and support the involvement of dopaminergic and noradrenergic transmission in hyperkinetic movement disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17348","type":"journal-article","created":{"date-parts":[[2024,9,21]],"date-time":"2024-09-21T04:08:11Z","timestamp":1726891691000},"page":"5094-5109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tetrabenazine, a vesicular monoamine transporter 2 inhibitor, inhibits vesicular storage capacity and release of monoamine transmitters in mouse brain tissue"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-7071","authenticated-orcid":false,"given":"P\u00e1l","family":"Tod","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology HUN\u2010REN Institute of Experimental Medicine  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2920-2641","authenticated-orcid":false,"given":"Anita","family":"Varga","sequence":"additional","affiliation":[{"name":"Pharmacology and Drug Safety Research Gedeon Richter Plc  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-3591","authenticated-orcid":false,"given":"Viktor","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Pharmacology and Drug Safety Research Gedeon Richter Plc  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9289-4715","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Lendvai","sequence":"additional","affiliation":[{"name":"Pharmacology and Drug Safety Research Gedeon Richter Plc  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3677-6260","authenticated-orcid":false,"given":"Roland","family":"P\u00e1lkov\u00e1cs","sequence":"additional","affiliation":[{"name":"Pharmacology and Drug Safety Research Gedeon Richter Plc  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-591X","authenticated-orcid":false,"given":"Be\u00e1ta","family":"Sperl\u00e1gh","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology HUN\u2010REN Institute of Experimental Medicine  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-4597","authenticated-orcid":false,"given":"E. 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