Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine signaling genes. Functionally, motivation was inversely related to excitability of NAc principal neurons. Furthermore, neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, Kv1.4. These results raise the prospect of targeting Kv1.4 gating in psychiatric conditions associated with motivational dysfunction.

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Published in eLife, v. 8, e47870, p. 1-22.

© 2019, O'Donovan et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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This work was supported by the National Institutes of Health grants K01DA031747, R01DA041513 (PIO), R00DA032681, R01DA044311 (JRT), T32DA016176 (RDC).

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Data generated or analysed during this study are included in the manuscript and supporting files.

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