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However, available treatments are limited with variable efficacy. Recently, preclinical studies show that glucagon\u2010like\u2010peptide\u20101 (GLP\u20101) and its analogue Exendin\u20104 (Ex4) potently reduce a range of alcohol intake behaviors, thus highlighting its potential as a treatment for alcohol use disorders. However, the neural mechanisms and sites of action mediating the effects of Ex4 on alcohol intake behaviors remain to be characterized. This study examined the ventral tegmental area (VTA) as a site of action for the effects of GLP\u20101 on alcohol intake.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Long\u2010Evans rats were given intermittent access to 20% alcohol and trained to nose poke for 20% alcohol. Rats received intra\u2010VTA injections of Ex4 (vehicle, 0.01, 0.05\u00a0<jats:italic>\u03bc<\/jats:italic>g), and the effects of VTA Ex4 on alcohol self\u2010administration, motivation, and relapse were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When compared to vehicle treatment, intra\u2010VTA Ex4 (0.01, 0.05\u00a0<jats:italic>\u03bc<\/jats:italic>g) delivery significantly reduced alcohol self\u2010administration, an effect that was particularly prominent in high alcohol drinkers. However, VTA Ex4 did not reduce reacquisition of alcohol self\u2010administration after extinction nor the motivation to obtain alcohol. Importantly, the lower dose of Ex4 (0.01\u00a0<jats:italic>\u03bc<\/jats:italic>g) used had no effect on food intake or locomotor activity, suggesting that the reduction in alcohol self\u2010administration observed was not secondary to caloric intake or motor deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, these findings provide support for the VTA as a key site of action for GLP\u20101 on alcohol self\u2010administration but not the reacquisition of alcohol self\u2010administration or motivation to work for alcohol.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14437","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T13:51:17Z","timestamp":1598622677000},"page":"2118-2129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Glucagon\u2010Like Peptide\u20101 Receptor Signaling in the Ventral Tegmental Area Reduces Alcohol 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