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These GABA<jats:sub>A<\/jats:sub>Rs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. \u03b14-Subunit constitutive knock-out mice (\u03b14<jats:sup>\u2212\/\u2212<\/jats:sup>) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABA<jats:sub>A<\/jats:sub>R \u03b14 subunits within the NAc. Local infusion of the \u03b14\u03b2\u03b4-GABA<jats:sub>A<\/jats:sub>R-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not \u03b14<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Finally, specific deletion of \u03b14-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that \u03b14-GABA<jats:sub>A<\/jats:sub>R-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its potentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine.<\/jats:p>","DOI":"10.1523\/eneuro.0236-23.2023","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T17:50:12Z","timestamp":1691517012000},"page":"ENEURO.0236-23.2023","source":"Crossref","is-referenced-by-count":1,"title":["\u03b14-Containing GABA<sub>A<\/sub>Receptors on DRD2 Neurons of the Nucleus Accumbens Mediate Instrumental Responding for Conditioned Reinforcers and Its Potentiation by Cocaine"],"prefix":"10.1523","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0250-1146","authenticated-orcid":false,"given":"Tom","family":"Macpherson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire 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