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Here, the M<\/jats:styled-content>5 receptor gene was bilaterally transfected into neurons in the ventral tegmental area (VTA<\/jats:styled-content>) or the adjacent rostromedial tegmental nucleus (RMT<\/jats:styled-content>g) in mice by means of a H<\/jats:styled-content>erpes simplex viral vector (HSV<\/jats:styled-content>) to increase the effect of endogenous acetylcholine. Three days after HSV<\/jats:styled-content>\u2010M<\/jats:styled-content>5 gene infusion in VTA<\/jats:styled-content> sites, morphine\u2010induced locomotion more than doubled at two doses, while saline\u2010induced locomotion was unaffected. When the HSV<\/jats:styled-content>\u2010M<\/jats:styled-content>5 gene was infused into the adjacent RMT<\/jats:styled-content>g, morphine\u2010induced locomotion was strongly inhibited. The sharp boundary between these opposing effects was found where tyrosine hydroxylase (TH<\/jats:styled-content>) and cholinesterase labelling decreases (\u22124.00\u00a0mm posterior to bregma). The same HSV<\/jats:styled-content>\u2010M<\/jats:styled-content>5 gene transfections in M<\/jats:styled-content>5 knockout mice induced even stronger inhibitory behavioural effects in RMT<\/jats:styled-content>g but more variability in VTA<\/jats:styled-content> sites due to stereotypy. The VTA<\/jats:styled-content> sites where HSV<\/jats:styled-content>\u2010M<\/jats:styled-content>5 increased morphine\u2010induced locomotion receive direct inputs from many RMT<\/jats:styled-content>g GAD<\/jats:styled-content>\u2010positive neurons, and from pontine C<\/jats:styled-content>hAT<\/jats:styled-content>\u2010positive neurons, as shown by cholera\u2010toxin B<\/jats:styled-content> retrograde tracing. Therefore, morphine\u2010induced locomotion was decreased by M<\/jats:styled-content>5 receptor gene expression in RMT<\/jats:styled-content>g GABA<\/jats:styled-content> neurons that directly inhibit VTA DA<\/jats:styled-content> neurons. Conversely, enhancing M<\/jats:styled-content>5 receptor gene expression on VTA DA<\/jats:styled-content> neurons increased morphine\u2010induced locomotion via cholinergic inputs.<\/jats:p>","DOI":"10.1111\/ejn.12279","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T05:28:49Z","timestamp":1371446929000},"page":"2774-2785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Cholinergic control of morphine\u2010induced locomotion in rostromedial tegmental nucleus versus ventral tegmental area sites"],"prefix":"10.1111","volume":"38","author":[{"given":"David I.","family":"Wasserman","sequence":"first","affiliation":[{"name":"Department of Psychology University of Toronto 100 St. George Street Toronto ON M5S 3G3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran G.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Toronto 100 St. George Street Toronto ON M5S 3G3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim J.","family":"Rashid","sequence":"additional","affiliation":[{"name":"Sick Children's Research Institute University of Toronto 555 University Avenue Toronto ON M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheena A.","family":"Josselyn","sequence":"additional","affiliation":[{"name":"Sick Children's Research Institute University of Toronto 555 University Avenue Toronto ON M5G 1X8 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Yeomans","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Toronto 100 St. George Street Toronto ON M5S 3G3 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22561"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2011.598386"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3370-12.2012"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162371899"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90343-M"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.06.007"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.812"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.93"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3884-09.2010"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00250.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"RC190","DOI":"10.1523\/JNEUROSCI.22-01-j0001.2002","article-title":"M5\u00a0muscarinic receptors are required for prolonged accumbal dopamine release after electrical stimulation of the pons in mice","volume":"22","author":"Forster G.L.","year":"2001","journal-title":"J. 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