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At early postnatal age, under sustained dopamine, this inhibitory response is followed by a slow recovery, resulting in dopamine inhibition reversal (DIR). In the present investigation, we aimed to get a better insight into the cellular mechanisms underlying DIR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We performed single\u2010unit extracellular recordings with a multi\u2010electrode array device and conventional patch\u2010clamp recordings on midbrain mouse slices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>While continuous dopamine (100\u00a0\u03bcM) perfusion gave rise to firing inhibition that recovered in 10 to 15\u00a0min, the same effect was not obtained with the D<jats:sub>2<\/jats:sub>receptor agonist quinpirole (100\u00a0nM). Moreover, firing inhibition caused by the GABA<jats:sub>B<\/jats:sub>receptor agonist baclofen (300\u00a0nM) was reversed by dopamine (100\u00a0\u03bcM), albeit D<jats:sub>2<\/jats:sub>receptors had been blocked by sulpiride (10\u00a0\u03bcM). Conversely, the block of the dopamine transporter (DAT) with cocaine (30\u00a0\u03bcM) prevented firing recovery by dopamine under GABA<jats:sub>B<\/jats:sub>receptor stimulation. Accordingly, in whole\u2010cell recordings from single cells, the baclofen\u2010induced outward current was counteracted by dopamine (100\u00a0\u03bcM) in the presence of sulpiride (10\u00a0\u03bcM), and this effect was prevented by the DAT antagonists cocaine (30\u00a0\u03bcM) and GBR12909 (2\u00a0\u03bcM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our results indicate that the DAT plays a major role in DIR, mediating it under conditions of sustained dopamine exposure, and point to DAT as an important target for pharmacological therapies leading to prolonged enhancement of the dopaminergic signal.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14422","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T16:09:38Z","timestamp":1529683778000},"page":"3534-3547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Reversal of 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