The contribution of medium spiny neuron subtypes in the nucleus accumbens core to compulsive-like ethanol drinking

NEUROPHARMACOLOGY

卷:187

Article

Sneddon, Elizabeth A. ; Schuh, Kristen M. ; Frankel, John W. ; Radke, Anna K.

关键词: Nucleus accumbens;    Drinking in the dark;    Dopamine;    Alcohol;    Aversion;    Reward;   

DOI  :  10.1016/j.neuropharm.2021.108497

来源: Elsevier

【 摘 要 】

Compulsive alcohol use, or drinking that persists despite negative or aversive consequences, is a defining characteristic of alcohol use disorder. Here, chemogenetic technology (i.e. Designer Receptors Exclusively Activated by Designer Drugs; DREADDs) was used to inhibit or excite the NAc core or selectively inhibit D-1-or D-2 receptor-expressing neurons in the NAc core to understand the role of the NAc core and how these sub populations of neurons may influence compulsive-like ethanol (EtOH) drinking using C57BL/6J, Drd1-cre, and Drd2-cre male and female mice. Compulsive-like EtOH drinking was modeled with a two-bottle choice, drinking in the dark paradigm. The major finding of this study was that mice decreased compulsive-like EtOH intake when the NAc core was inhibited and there was no change of EtOH + quinine intake when the NAc core was excited. Interestingly, inhibition of D-1-or D-2 receptor-expressing neurons did not alter compulsive-like EtOH intake. Control experiments showed that NAc core excitation and selective inhibition of D-1-or D-2-receptor-expressing neurons had no effect on baseline EtOH drinking, intake of water, or intake of quinine-adulterated water. CNO reduced amphetamine-induced locomotion in the D-1-(CRE+) (but not the D-2(CRE+)) group in a control experiment. Finally, pharmacological antagonism of D-1 and D-2 receptors together, but not separately, reduced quinine resistant EtOH drinking. These results suggest that the NAc core is a critical region involved in compulsive like EtOH consumption, and that both D-1-and D-2 receptor-expressing medium spiny neurons participate in controlling this behavior.

【 授权许可】

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