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Ethanol acutely increases dopamine neuron excitability, and psychostimulants such as cocaine or methamphetamine increase extracellular dopamine through inhibition of uptake through the dopamine transporter (DAT) and\/or vesicular monoamine transporter 2 (VMAT2). Psychostimulants also depress dopamine neuron activity by enhancing dendritic dopamine neurotransmission. Here, we show that mice with a previous history of ethanol drinking are more sensitive to the locomotor\u2010stimulating effects of a high dose (5\u00a0mg\/kg), but not lower doses (1 and 3\u00a0mg\/kg) of methamphetamine or any tested dose of cocaine (3, 10, and 18\u00a0mg\/kg), compared with water\u2010drinking controls. We next investigated the impact of a history of ethanol drinking, in a separate group of mice, on methamphetamine\u2010 or cocaine\u2010induced enhancement of dendritic dopamine transmission using whole\u2010cell voltage clamp electrophysiology in mouse brain slices. Methamphetamine, applied at a concentration (10\u00a0\u03bcM) that affects both DAT and VMAT2, enhanced D2 receptor\u2010mediated inhibitory postsynaptic currents (D2\u2010IPSCs) in both groups, but this effect was blunted in mice with a history of ethanol drinking. As methamphetamine action at VMAT2 disrupts dopamine neurotransmission, these results may suggest enhanced action of methamphetamine at VMAT2. Furthermore, there were no differences in low\u2010dose methamphetamine or cocaine\u2010induced enhancement of D2\u2010IPSCs, suggesting intact DAT function. Disruption of methamphetamine\u2010induced enhancement of dendritic dopamine transmission would result in decreased inhibition of dopamine neurons, ultimately increasing downstream release and the behavioral effects of methamphetamine.<\/jats:p>","DOI":"10.1111\/adb.12763","type":"journal-article","created":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T01:19:55Z","timestamp":1557191995000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A history of ethanol drinking increases locomotor stimulation and blunts enhancement of dendritic dopamine transmission by methamphetamine"],"prefix":"10.1111","volume":"25","author":[{"given":"Christopher W.","family":"Tschumi","sequence":"first","affiliation":[{"name":"Aging and Metabolism Research Program Oklahoma Medical Research Foundation  Oklahoma City Oklahoma USA"},{"name":"Department of Cellular and Integrative Physiology University of Texas Health Science Center at 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