{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:56:02Z","timestamp":1777593362278,"version":"3.51.4"},"reference-count":98,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T00:00:00Z","timestamp":1579910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["08224"],"award-info":[{"award-number":["08224"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["0848-05A1"],"award-info":[{"award-number":["0848-05A1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["084854"],"award-info":[{"award-number":["084854"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["061838"],"award-info":[{"award-number":["061838"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000089","name":"Office of International Science and Engineering","doi-asserted-by":"publisher","award":["1545803"],"award-info":[{"award-number":["1545803"]}],"id":[{"id":"10.13039\/100000089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic \u03b11-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic \u03b11-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that \u03b11-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an \u03b11-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of \u03b11-ARs persists after a 7-day withdrawal period. In contrast, the modulation of \u03b11-ARs on GABA neurotransmission, shown by decreases in IPSCs\u2019 amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that \u03b11-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of \u03b11-ARs\u2019 function on glutamate release and protein kinase C (PKC) activation. \u03b11-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.<\/jats:p>","DOI":"10.3390\/ijms21030790","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T07:41:11Z","timestamp":1580110871000},"page":"790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization"],"prefix":"10.3390","volume":"21","author":[{"given":"Maria Carolina","family":"Velasquez-Martinez","sequence":"first","affiliation":[{"name":"Grupo de Neurociencias y Comportamiento, Departamento de Ciencias B\u00e1sicas, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga 680006, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bermary","family":"Santos-Vera","sequence":"additional","affiliation":[{"name":"Department of Biology, Cayey Campus, University of Puerto Rico, Cayey, PR 00737, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Velez-Hernandez","sequence":"additional","affiliation":[{"name":"Department of Biological and Health Sciences, Texas A&amp;M University-Kingsville, Kingsville, TX 78363, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Vazquez-Torres","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00925, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A.","family":"Jimenez-Rivera","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00925, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/BF02147990","article-title":"Localization of monoamines in the lower brain stem","volume":"20","author":"Dahlstrom","year":"1964","journal-title":"Experientia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-201X.1971.tb10998.x","article-title":"Stereotaxic mapping of the monoamine pathways in the rat brain","volume":"367","author":"Ungerstedt","year":"1971","journal-title":"Acta Physiol. 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