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. 2024 Oct 23;112(20):3470-3485.e12.
doi: 10.1016/j.neuron.2024.07.018. Epub 2024 Aug 16.

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity

Guilian Tian  1 , Katrina Bartas  2 , May Hui  1 , Lingxuan Chen  1 , Jose J Vasquez  1 , Ghalia Azouz  1 , Pieter Derdeyn  2 , Rían W Manville  3 , Erick L Ho  1 , Amanda S Fang  1 , Yuan Li  1 , Isabella Tyler  1 , Vincent Setola  4 , Jason Aoto  5 , Geoffrey W Abbott  3 , Kevin T Beier  6
Affiliations

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity

Guilian Tian et al. Neuron. .

Abstract

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.

Keywords: behavioral vulnerability; carnosic acid; chemogenetics; cocaine; dopamine; drug abuse; globus pallidus; intrinsic excitability; rabies virus; ventral tegmental area; voltage-gated potassium channels.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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References

    1. Bromberg-Martin ES, Matsumoto M, and Hikosaka O (2010). Dopamine in Motivational Control: Rewarding, Aversive, and Alerting. Neuron 68, 815–834. 10.1016/j.neuron.2010.11.022. - DOI - PMC - PubMed
    1. Schultz W (2007). Multiple Dopamine Functions at Different Time Courses. Annu Rev Neurosci 30, 259–288. 10.1146/annurev.neuro.28.061604.135722. - DOI - PubMed
    1. Ungless MA, Argilli E, and Bonci A (2010). Effects of stress and aversion on dopamine neurons: Implications for addiction. Preprint, https://doi.org/10.1016/j.neubiorev.2010.04.006 10.1016/j.neubiorev.2010.04.006. - DOI - PubMed
    1. Wise RA (2004). Dopamine, learning and motivation. Nat Rev Neurosci 5, 483–494. 10.1038/nrn1406. - DOI - PubMed
    1. Kalivas PW, and Volkow ND (2005). The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162, 1403–1413. 10.1176/appi.ajp.162.8.1403. - DOI - PubMed

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