Neurotransmitter Receptor Influence on Behavior Open access

Dopamine dips during unrewarded actions promote punishment-resistant reward seeking

Nkatha Mwenda, Jacob A. Nadel, Tong Shen, Jillian L. Seiler and 1 more

bioRxiv (Cold Spring Harbor Laboratory) | Aug 3, 2026

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D dopamine dips suppress learning from unrewarded actions, consistent with policy-based accounts of dopamine function, and optogenetically mimicking these dips accelerated punishment resistance in females and males.

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ABSTRACT Punishment-resistant reward-seeking, a hallmark of addiction, is less prominent in females than males. We found that chronic estradiol manipulations increased punishment resistance in female mice without increasing dopamine peaks on rewarded actions as expected, instead exaggerating dopamine dips on unrewarded actions; optogenetically mimicking these dips accelerated punishment resistance in females and males. These results suggest dopamine dips suppress learning from unrewarded actions, consistent with policy-based accounts of dopamine function.

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Nkatha Mwenda

first | Northwestern University | ORCID 0000-0001-5411-9451

Jacob A. Nadel

middle | Northwestern University | ORCID 0000-0002-7611-2434

Tong Shen

middle | Northwestern University

Jillian L. Seiler

middle | Northwestern University | ORCID 0000-0003-4430-4797

Talia N. Lerner

last | Northwestern University | ORCID 0000-0002-3875-0654

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BibTeX

@article{Mwenda2026Dopamine,
  title = {Dopamine dips during unrewarded actions promote punishment-resistant reward seeking},
  author = {Nkatha Mwenda and Jacob A. Nadel and Tong Shen and Jillian L. Seiler and Talia N. Lerner},
  journal = {bioRxiv (Cold Spring Harbor Laboratory)},
  year = {2026},
  doi = {10.64898/2026.08.01.742224},
  url = {https://doi.org/10.64898/2026.08.01.742224}
}

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