{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:51:32Z","timestamp":1790693492851,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011085","name":"David R. Bloom Center for Pharmacy, Hebrew University of Jerusalem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001739","name":"National Institute for Psychobiology in Israel, Hebrew University of Jerusalem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001739","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elevated dopamine (DA) levels in the reward system underlie various drug\u2010related behaviors, including addiction. As a major DA source in the reward system, the ventral tegmental area (VTA) is highly regulated by GABAergic inputs projected from different brain regions. It was previously shown that cocaine exposure reduces GABA<jats:sub>A<\/jats:sub>\u2010mediated inhibitory postsynaptic currents (IPSCs) in VTA DA neurons; however, the specific GABAergic input underlying this inhibitory effect remains unknown. Here, using optogenetics, we separately activate and characterize different GABAergic afferents innervating the VTA, focusing on the rostromedial tegmental nucleus (RMTg) and the nucleus accumbens (NAc). GABA<jats:sub>A<\/jats:sub>\u2010mediated IPSCs were recorded from VTA DA neurons, and the effect of DA\u2010induced inhibition was measured in an afferent\u2010specific manner. In addition, to examine the effect of enhanced GABAergic tone on the rewarding properties of cocaine, we exogenously activated the different GABAergic inputs during the acquisition phase of cocaine conditioned place preference (CPP). We found that acute cocaine exposure strongly attenuates GABA<jats:sub>A<\/jats:sub>\u2010mediated IPSCs in VTA DA neurons from both inhibitory sources. Furthermore, exogenous light activation of both RMTg and NAc afferents in the VTA during the acquisition of cocaine\u2010CPP significantly reduced the rewarding properties of cocaine. This behavioral observation was correlated with the reduction in the neuronal activity of VTA DA neurons as measured by the expression of c\u2010fos. Together, these results emphasize the critical role of these GABAergic inputs to the VTA in modulating and potentially interrupting cocaine reward.<\/jats:p>","DOI":"10.1111\/adb.13026","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T06:24:40Z","timestamp":1614407080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["GABAergic projections to the ventral tegmental area govern cocaine\u2010conditioned reward"],"prefix":"10.1111","volume":"26","author":[{"given":"Moriya","family":"Weitz","sequence":"first","affiliation":[{"name":"Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Khayat","sequence":"additional","affiliation":[{"name":"Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-2957","authenticated-orcid":false,"given":"Rami","family":"Yaka","sequence":"additional","affiliation":[{"name":"Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.45"},{"issue":"4","key":"e_1_2_7_3_1","first-page":"445","article-title":"Brain mechanisms of drug reward and euphoria","volume":"3","author":"Wise RA","year":"1985","journal-title":"Psychiatr Med"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2234"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35094560"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187801"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2367"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.017"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3381"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20668"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0012-07.2007"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510715103"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11527"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05860"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902350304"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.02.001"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1384-11.2011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21891"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3370-12.2012"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.04.030"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.01.046"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.02.016"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.02.015"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-19-08003.1998"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13879"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1504-11.2011"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4482"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12998.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1151\/spp05314"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.11.045"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06479.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3145"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1037\/0033-295X.94.4.469"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ps.40.020189.001203"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(80)90166-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.103.6.1327"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00429012"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019136"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-02-00796.1997"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-2-00163.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.6.2911"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.02.029"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1524-14.2015"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1237059"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/35079077"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1312-04.2004"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.2741\/1198"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(00)00286-0"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.10.039"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.190"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.08.041"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.13026","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T02:21:08Z","timestamp":1692670868000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.13026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/adb.13026"],"URL":"https:\/\/doi.org\/10.1111\/adb.13026","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]},"assertion":[{"value":"2020-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13026"}}