1. Indirect Medium Spiny Neurons in the Dorsomedial Striatum Regulate Ethanol-Containing Conditioned Reward Seeking.
- Author
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Sa-Ik Hong, Seungwoo Kang, Jiang-Fan Chen, and Doo-Sup Choi
- Subjects
GLOBUS pallidus ,NEURONS ,SUCROSE ,ADENOSINES - Abstract
Adenosine 2A receptor (A
2A R)-containing indirect medium spiny neurons (iMSNs) in the dorsomedial striatum (DMS) contribute to reward-seeking behaviors. However, those roles for ethanol-seeking behaviors remain unknown. To investigate ethanol-seeking behaviors, we used an ethanol-containing reward (10% ethanol and 10% sucrose solution; 10E10S). Upon conditioning with 10E10S, mice that initially only preferred 10% sucrose, not 10E10S, showed a stronger preference for 10E10S. Then, we investigated whether the manipulation of the DMS-external globus pallidus (GPe) iMSNs circuit alters the ethanol-containing reward (10E10S) seeking behaviors using the combination of pharmacologic and optogenetic approaches. DMS A2A R activation dampened operant conditioning-induced ethanolcontaining reward, whereas A2A R antagonist abolished the effects of the A2A R agonist and restored ethanol-containing reward-seeking. Moreover, pre-ethanol exposure potentiated the A2A R-dependent reward-seeking. Interestingly, mice exhibiting ethanol-containing reward-seeking showed the reduction of the DMS iMSNs activity, suggesting that disinhibiting iMSNs decreases reward-seeking behaviors. In addition, we found that A2A R activation reversed iMSNs neural activity in the DMS. Similarly, optogenetic stimulation of the DMS-GPe iMSNs reduced ethanol-containing reward-seeking, whereas optogenetic inhibition of the DMS-GPe iMSNs reversed this change. Together, our study demonstrates that DMS A2A R and iMSNs regulate ethanol-containing reward-seeking behaviors. [ABSTRACT FROM AUTHOR]- Published
- 2019
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