{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:03:29Z","timestamp":1790499809633,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T00:00:00Z","timestamp":1457395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003451","name":"Euskal Herriko Unibertsitatea","doi-asserted-by":"publisher","award":["IT 747\u201013"],"award-info":[{"award-number":["IT 747\u201013"]}],"id":[{"id":"10.13039\/501100003451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>L\u2010DOPA is still the most efficacious pharmacological treatment for Parkinson's disease. However, in the majority of patients receiving long\u2010term therapy with L\u2010DOPA, its efficacy is compromised by motor complications, notably L\u2010DOPA\u2010induced dyskinesia. Evidence suggests that the serotonergic system is involved in the therapeutic and the side effects of L\u2010DOPA. Here, we investigate if long\u2010term L\u2010DOPA treatment alters the activity of the dorsal raphe nucleus (DRN) and its responses to serotonergic drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We measured the responses of serotonergic neurons to acute and chronic L\u2010DOPA treatment using<jats:italic>in vivo<\/jats:italic>electrophysiological single unit\u2010extracellular recordings in the 6\u2010OHDA\u2010lesion rat model of<jats:styled-content style=\"fixed-case\">Parkinson's disease<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The results showed that neither acute nor chronic L\u2010DOPA administration (6\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00a0s.c.) altered the properties of serotonergic\u2010like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L\u2010DOPA\u2010induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5\u2010HT<jats:sub>1A<\/jats:sub>receptor agonist 8\u2010OH\u2010DPAT (0.0625\u201316\u00a0\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v.) was preserved. Nonetheless, L\u2010DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125\u20138\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.v) to inhibit DRN neuron firing rate in dyskinetic animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Although serotonergic neurons are involved in the dopaminergic effects of L\u2010DOPA, we provide evidence that the effect of L\u2010DOPA is not related to changes of the activity of DRN neurons. Rather, L\u2010DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v173.13\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v173.13\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13447","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T10:27:16Z","timestamp":1453717636000},"page":"2135-2146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The acute and long\u2010term L\u2010DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6\u2010OHDA lesioned rats"],"prefix":"10.1111","volume":"173","author":[{"given":"C","family":"Miguelez","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Dentistry University of the Basque Country (UPV\/EHU) Leioa Spain"},{"name":"Department of Pharmacology, Faculty of Pharmacy University of the Basque Country (UPV\/EHU) Vitoria\u2010Gasteiz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Navailles","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"De Deurwaerd\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Bordeaux Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"},{"name":"CNRS, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Ugedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Dentistry University of the Basque Country (UPV\/EHU) Leioa Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22589"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13355"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042652"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2013.10.002"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08202.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.10343"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2079-07.2007"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm082"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90240-G"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2007.01.013"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)00921-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000031424.51127.2B"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.05.005"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20630"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.04.027"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145707008383"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00170162"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00227-A"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702510"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0022-3565(25)31520-X","article-title":"Role of monoamine neural systems in L\u2010dihydroxyphenylalanine\u2010stimulated activity","volume":"208","author":"Hollister AS","year":"1979","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.09.011"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.01.012"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.05.021"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.12003FP"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00184.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.05.019"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"issue":"1","key":"e_1_2_11_31_1","first-page":"120","article-title":"Preferential loss of serotonin markers in caudate versus putamen in Parkinson's disease","volume":"131","author":"Kish SJ","year":"2008","journal-title":"Brain"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(02)00377-9"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-1030-6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06556.x"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-2012-120103"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00050-8"},{"key":"e_1_2_11_37_1","first-page":"1191","article-title":"Serotonergic antidepressant drugs and L\u2010dopa\u2010induced dyskinesias in Parkinson's disease","volume":"131","author":"Mazzucchi S","year":"2014","journal-title":"Acta Neurol Scand"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.12.003"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024679"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1017\/S146114571000043X"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.11.016"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2014.00021"},{"key":"e_1_2_11_44_1","volume-title":"Society for Neuroscience","author":"Miguelez C","year":"2014"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.06.017"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn235"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.11.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.01.012"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-011-8230-0"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn400046e"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07292.x"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02246453"},{"key":"e_1_2_11_53_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-3565(25)28846-2","article-title":"Pharmacological estimation of drug\u2010receptor dissociation constants. Statistical evaluation. I. Agonists","volume":"177","author":"Parker RB","year":"1971","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1143"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.05.028"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.06.015"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.08.009"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07675.x"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(11)70039-6"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22097"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-10-49"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.218966"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu409"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199902250-00034"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.12.051"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200105080-00015"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-014-1669-9"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711839105"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2007.05.033"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13447","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13447","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.13447","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13447","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T06:48:45Z","timestamp":1748760525000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,8]]},"references-count":68,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/bph.13447"],"URL":"https:\/\/doi.org\/10.1111\/bph.13447","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,8]]},"assertion":[{"value":"2015-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}