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Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge‐Like Alcohol Drinking in Mice
Author(s) -
Purohit Kush,
Parekh Puja K.,
Kern Joseph,
Logan Ryan W.,
Liu Zheng,
Huang Yanhua,
McClung Colleen A.,
Crabbe John C.,
Ozburn Angela R.
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13626
Subject(s) - nucleus accumbens , binge drinking , saccharin , alcohol , neuroscience , chemistry , pharmacology , disulfiram , psychology , medicine , dopamine , alcohol consumption , biochemistry
Background Chronic alcohol intake leads to long‐lasting changes in reward‐ and stress‐related neuronal circuitry. The nucleus accumbens ( NA c) is an integral component of this circuitry. Here, we investigate the effects of DREADD s (Designer Receptors Exclusively Activated by Designer Drugs) on neuronal activity in the NA c and binge‐like drinking. Methods C57 BL /6J mice were stereotaxically injected with AAV 2 hS yn‐ HA hM 3Dq, ‐ hM 4Di, or ‐ eGFP bilaterally into NA c [core + shell, core or shell]. We measured clozapine‐ n ‐oxide (CNO)‐induced changes in NA c activity and assessed binge‐like ethanol (EtOH) or tastant/fluid intake in a limited access Drinking in the Dark ( DID ) schedule. Results We found that CNO increased NA c firing in hM 3Dq positive cells and decreased firing in hM 4Di cells, confirming the efficacy of these channels to alter neuronal activity both spatially and temporally. Increasing NA c core + shell activity decreased binge‐like drinking without altering intake of other tastants. Increasing activity specifically in the NA c core reduced binge‐like drinking, and decreasing activity in the NA c core increased drinking. Manipulation of NA c shell activity did not alter DID . Thus, we find that increasing activity in the entire NA c, or just the NA c core is sufficient to decrease binge drinking. Conclusions We conclude that the reduction in EtOH drinking is not due to general malaise, altered perception of taste, or reduced calorie‐seeking. Furthermore, we provide the first evidence for bidirectional control of NA c core and binge‐like drinking. These findings could have promising implications for treatment.