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Using a rodent model of PD, we reported alterations in glutamate synapses in the striatum and substantia nigra following dopamine (DA) loss. We hypothesize that DA loss will result in increased anxiety\u2010related behaviours and that this will be associated with alterations in glutamate synapses and transporters within the medial prefrontal cortex (mPFC). Following 4\u00a0weeks of progressive 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) administration, there was an increase in anxiety\u2010related behaviours and a 78% decrease in plasma corticosterone levels versus the vehicle (VEH)\u2010treated mice. This was associated with a 30% decrease in the density of dendritic spines in Layers Il\/Ill, and a 53% decrease in the density of glutamate immuno\u2010gold labelling within vesicular glutamate transporter 1 (Vglut1)\u2010labelled nerve terminals and spines, with no change within vesicular glutamate transporter 2 (Vglut2) positive terminals\/spines in the MPTP versus VEH groups. Our prior work determined that a decrease in striatal glutamate terminal density was associated with an increase in extracellular glutamate levels. There was an increase in protein expression of Vglut1 (40%), Vglut2 (37%) and glutamate aspartate transporter (GLAST) (225%), and a decrease in glutamate transporter 1 (GLT\u20101) (50%) and excitatory amino acid carrier 1 (EAAC1) (51%), in the MPTP versus VEH groups within the mPFC. These data suggest that the decrease in dendritic spines within the mPFC following nigrostriatal DA loss may be due to increased extracellular glutamate levels (decrease in glutamate transporters), leading to an increase in anxiety\u2010related behaviours.<\/jats:p>","DOI":"10.1111\/ejn.16577","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T06:34:49Z","timestamp":1729492489000},"page":"6195-6215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dopamine loss alters glutamate synapses and transporters in the medial prefrontal cortex and anxiety\u2010related behaviour in a male MPTP rodent model of Parkinson's disease"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-8748","authenticated-orcid":false,"given":"Cindy","family":"Moore","sequence":"first","affiliation":[{"name":"VA Medical Center\/Portland  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda L.","family":"Helms","sequence":"additional","affiliation":[{"name":"VA Medical Center\/Portland  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle A.","family":"Nipper","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lila C.","family":"Winfrey","sequence":"additional","affiliation":[{"name":"VA Medical Center\/Portland  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Finn","sequence":"additional","affiliation":[{"name":"VA Medical Center\/Portland  Portland Oregon USA"},{"name":"Department of Behavioral Neuroscience Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3908-0795","authenticated-orcid":false,"given":"Charles K.","family":"Meshul","sequence":"additional","affiliation":[{"name":"VA Medical Center\/Portland  Portland Oregon USA"},{"name":"Department of Behavioral Neuroscience Oregon Health &amp; Science University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.baga.2015.06.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42691-z"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2891-04.2004"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.04.031"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.09.033"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01660-X"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(76)90078-0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(73)90175-5"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(90)90184-O"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201607305"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13198"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.03.006"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.06.006"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.07.031"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(92)90036-8"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2014.07.015"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.748165"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2023.103883"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.07.004"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90038-8"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13187"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145712000892"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.10.004"},{"key":"e_1_2_11_25_1","first-page":"394","article-title":"Differential change in neuroactive steroid sensitivity during ethanol withdrawal","volume":"292","author":"Finn D. 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