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Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors

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Abstract

Corticotropin-releasing factor (CRF) in the anterior bed nucleus of the stria terminalis (aBNST) is associated with chronic stress and avoidance behavior. However, CRF + BNST neurons project to reward- and motivation-related brain regions, suggesting a potential role in motivated behavior. We used chemogenetics to selectively activate CRF+ aBNST neurons in male and female CRF-ires-Cre mice during an effort-related choice task and a concurrent choice task. In both tasks, mice were given the option either to exert effort for high value rewards or to choose freely available low value rewards. Acute chemogenetic activation of CRF+ aBNST neurons reduced barrier climbing for a high value reward in the effort-related choice task in both males and females. Furthermore, acute chemogenetic activation of CRF+ aBNST neurons also reduced effortful lever pressing in high-performing males in the concurrent choice task. These data suggest a novel role for CRF+ aBNST neurons in effort-based decision and motivation behaviors.

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Fig. 1: Virally-mediated DREADD expression was confirmed to localize in the anterior bed nucleus of the stria terminalis (aBNST), a region associated with avoidance behaviors.
Fig. 2: Chemogenetic activation of CRF + BNST neurons reduced selection of the high reward (HR) arm in a Y-maze barrier task.
Fig. 3: Chemogenetic activation of CRF + BNST neurons decreased lever pressing for sucrose pellets in high-performing males.
Fig. 4: Chemogenetic activation of CRF + BNST neurons increases appetite and does not affect sucrose preference.

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Funding

This work was supported by National Institutes of Mental Health (NIMH) Grant R01 MH123544 (BAS, TAR).

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IM, AB, BAS, and TAR conceived of the experiments. IM, AB, KC, AP, MM, JS, TL, RS, MP, PH conducted or assisted with experiments. IM wrote the first draft of the paper, and BAS and TAR revised.

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Correspondence to Benjamin Adam Samuels.

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Maita, I., Bazer, A., Chae, K. et al. Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors. Neuropsychopharmacol. 49, 377–385 (2024). https://doi.org/10.1038/s41386-023-01646-9

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