Mesolimbic dopamine release precedes actively sought aversive stimuli in mice

Yosuke Yawata, Yu Shikano, Jun Ogasawara, Kenichi Makino, Tetsuhiko Kashima, Keiko Ihara, Airi Yoshimoto, Shota Morikawa, Sho Yagishita, Kenji F. Tanaka and Yuji Ikegaya ()
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Yosuke Yawata: The University of Tokyo
Yu Shikano: Keio University School of Medicine
Jun Ogasawara: The University of Tokyo
Kenichi Makino: The University of Tokyo
Tetsuhiko Kashima: The University of Tokyo
Keiko Ihara: Keio University School of Medicine
Airi Yoshimoto: The University of Tokyo
Shota Morikawa: The University of Tokyo
Sho Yagishita: The University of Tokyo
Kenji F. Tanaka: Keio University School of Medicine
Yuji Ikegaya: The University of Tokyo

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract In some models, animals approach aversive stimuli more than those housed in an enriched environment. Here, we found that male mice in an impoverished and unstimulating (i.e., boring) chamber without toys sought aversive air puffs more often than those in an enriched chamber. Using this animal model, we identified the insular cortex as a regulator of aversion-seeking behavior. Activation and inhibition of the insular cortex increased and decreased the frequencies of air-puff self-stimulation, respectively, and the firing patterns of insular neuron ensembles predicted the self-stimulation timing. Dopamine levels in the ventrolateral striatum decreased with passive air puffs but increased with actively sought puffs. Around 20% of mice developed intense self-stimulation despite being offered toys, which was prevented by administering opioid receptor antagonists. This study establishes a basis for comprehending the neural underpinnings of usually avoided stimulus-seeking behaviors.

Date: 2023
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DOI: 10.1038/s41467-023-38130-3

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