{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T22:36:57Z","timestamp":1789339017420,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T00:00:00Z","timestamp":1332201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The mesocorticolimbic dopamine system mediates the reinforcing effects of salient stimuli, including drugs of abuse. Nondependent chronic alcohol consumption modifies this system, resulting in an increased number of spontaneously active dopamine neurons in the posterior ventral tegmental area (<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>) of alcohol\u2010preferring (<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>) rats. Enhanced responses of postsynaptic glutamate receptors may contribute to the increase in active dopamine neurons. Thus, excitations of putative dopamine neurons to locally applied<jats:italic><jats:styled-content style=\"fixed-case\">N<\/jats:styled-content><\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartic acid (<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>; glutamate receptor subtype agonist) were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>rats were assigned to alcohol na\u00efve (water only) or alcohol drinking (continuous access to 15% alcohol and water for 8 consecutive weeks) groups. Responses of 23 putative dopamine neurons from na\u00efve rats and 19 putative dopamine neurons from drinking rats were assessed in vivo using microiontophoretically applied<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>. Current\u2013response curves for firing frequency and burst activity were constructed using nonlinear mixed effects models. Between\u2010group comparisons were made for<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>(effective current producing a half maximal excitatory response),<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>max<\/jats:sub>(maximal excitatory effect), and<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content><jats:sub>DB<\/jats:sub>(the current at which depolarization block\u2014marked decrease in neuronal activity\u2014occurred).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Drinking<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>rats steadily consumed alcohol over the 8\u2010week protocol and did not exhibit signs of dependence or withdrawal. Putative dopamine neurons from drinking rats exhibited resistance to depolarization block (higher<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content><jats:sub>DB<\/jats:sub>values) and required larger doses of<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>to elicit moderate excitatory responses (higher<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content><jats:sub>50<\/jats:sub>values), consistent with decreased receptor affinity. Maximal excitatory responses (<jats:styled-content style=\"fixed-case\">E<\/jats:styled-content><jats:sub>max<\/jats:sub>) did not differ between the groups, consistent with no change in receptor number. Blood alcohol was at undetectable levels at the time of experimentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>receptor sensitivity is decreased on posterior<jats:styled-content style=\"fixed-case\">VTA<\/jats:styled-content>putative dopamine neurons in<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>rats on a nondependent schedule of alcohol consumption. Mechanisms underlying increased spontaneous dopamine neuron activity may be independent of changes in<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>receptor function. Decreased<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>receptor sensitivity may precede the development of dependence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01762.x","type":"journal-article","created":{"date-parts":[[2012,3,21]],"date-time":"2012-03-21T20:00:22Z","timestamp":1332360022000},"page":"1710-1719","source":"Crossref","is-referenced-by-count":12,"title":["Decreased Sensitivity of<scp>NMDA<\/scp>Receptors on Dopaminergic Neurons from the Posterior Ventral Tegmental Area Following Chronic Nondependent Alcohol Consumption"],"prefix":"10.1111","volume":"36","author":[{"given":"Griffin J.","family":"Fitzgerald","sequence":"first","affiliation":[{"name":"Department of Psychiatry Indiana University School of Medicine Indianapolis Indiana"},{"name":"Department of Psychology Psychobiology of Addictions Graduate Program Indiana University\u2010Purdue University Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Morzorati","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702284"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300730"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.050963"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00654-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.12.004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2961-09.2009"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1999.tb04082.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70052216.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00255-X"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(88)80073-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(83)90150-8"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4053-09.2009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90598-9"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1991.tb02048.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.00985.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2011.02.304"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01132-3"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(03)00186-4"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1103"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01009.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1943-10.2010"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)90381-6"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90307-7"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-11-02877.1984"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90135-5"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.09-10-03463.1989"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.111419"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00824.2007"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520290500138422"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.05.004"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00079.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019136"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1329209"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67020601.x"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890030105"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02783.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1046\/j.1471-4159.1997.69020662.x","article-title":"Eating\u2010induced dopamine release from mesolimbic neurons is mediated by NMDA receptors in the ventral tegmental area: a dual\u2010probe microdialysis study","volume":"69","author":"Kwint H\u2010F","year":"1997","journal-title":"J Neurochem"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00189.2007"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117069"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1526-08.2008"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91486-K"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.698"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2006.00113.x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2010.02.009"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(86)90010-8"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890210403"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890100208"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209532200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00679-K"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"e_1_2_6_52_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0026-895X(25)09563-X","article-title":"Glycine site\u2010directed agonists reverse the actions of ethanol at the N\u2010methyl\u2010d\u2010aspartate receptor","volume":"38","author":"Rabe CS","year":"1990","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1319-03.2004"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.80.1.1"},{"key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0022-3565(24)38077-2","article-title":"Ethanol exposure differentially alters central monoamine neurotransmission in alcohol\u2010preferring versus \u2010nonpreferring rats","volume":"288","author":"Smith AD","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5562-08.2009"},{"key":"e_1_2_6_57_1","unstructured":"1985 John Wiley & Sons New York NY TW Stone Microiontophoresis and Pressure Ejection"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2008.00749.x"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90076-E"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.059790"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.62.03.0008"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.2307\/2532734"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90459-2"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890130310"},{"key":"e_1_2_6_65_1","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0022-3565(25)39420-6","article-title":"Oral alcohol self\u2010administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants","volume":"267","author":"Weiss F","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02605.1996"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.02.064"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00859-1"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.99"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90861-Z"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5282-03.2004"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.10.013"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813415106"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1530-0277.2012.01762.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1530-0277.2012.01762.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T17:14:22Z","timestamp":1742750062000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1530-0277.2012.01762.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,20]]},"references-count":72,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1111\/j.1530-0277.2012.01762.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1530-0277.2012.01762.x","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,20]]}}}