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Activation of Kv7 channels normalizes hyperactivity of the VTA-NAcLat circuit and attenuates methamphetamine-induced conditioned place preference and sensitization in mice

Molecular Psychiatry volume 28, pages 5183–5194 (2023)Cite this article

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Abstract

The brain circuit projecting from the ventral tegmental area (VTA) to the nucleus accumbens lateral shell (NAcLat) has a key role in methamphetamine (MA) addiction. As different dopamine (DA) neuron subpopulations in the VTA participate in different neuronal circuits, it is a challenge to isolate these DA neuron subtypes. Using retrograde tracing and Patch-seq, we isolated DA neurons in the VTA-NAcLat circuit in MA-treated mice and performed gene expression profiling. Among the differentially expressed genes, KCNQ genes were dramatically downregulated. KCNQ genes encode Kv7 channel proteins, which modulate neuronal excitability. Injection of both the Kv7.2/3 agonist ICA069673 and the Kv7.4 agonist fasudil into the VTA attenuated MA-induced conditioned place preference and locomotor sensitization and decreased neuronal excitability. Increasing Kv7.2/3 activity decreased neural oscillations, synaptic plasticity and DA release in the VTA-NacLat circuit in MA-treated mice. Furthermore, overexpression of only Kv7.3 channels in the VTA-NacLat circuit was sufficient to attenuate MA-induced reward behavior and decrease VTA neuron excitability. Activation of Kv7 channels in the VTA may become a novel treatment strategy for MA abuse.

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Fig. 1: Anatomical organization of VTA neurons projecting to the NAcLat.
Fig. 2: Single-cell RNA-seq analysis of DA neurons in the VTA-NAcLat circuit in mice treated with MA.
Fig. 3: Activation of Kv7 channels reduces the addictive potential of MA and modulates the cellular excitability of VTA neurons in MA-treated mice.
Fig. 4: Activation of Kv7.2/3 channels reduces neuronal oscillations and the levels of Arc in MA-treated mice.
Fig. 5: Effects of Kv7.2/3 channel activation on DA release into the NAcLat and synaptic plasticity in the VTA-NAcLat circuit.
Fig. 6: Overexpression of Kv7.3 channels rescues behavioral and electrophysiological changes induced by MA in mice.

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References

  1. Gonzales R, Mooney L, Rawson RA. The methamphetamine problem in the United States. Annu Rev Public Health. 2010;31:385–98.

    PubMed  PubMed Central  Google Scholar 

  2. UNODC. United Nations Office on Drug and Crime (UNODC) United Nations. World Drug Report. 2022.

  3. Bjorklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci. 2007;30:194–202.

    PubMed  Google Scholar 

  4. Ikemoto S. Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res Rev. 2007;56:27–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Nestler EJ. Is there a common molecular pathway for addiction? Nat Neurosci. 2005;8:1445–9.

    CAS  PubMed  Google Scholar 

  6. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA. 1988;85:5274–8.

    PubMed  PubMed Central  Google Scholar 

  7. Johnson SW, North RA. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci. 1992;12:483–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Di Chiara G. Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res. 2002;137:75–114.

    PubMed  Google Scholar 

  9. Fallon JH. Collateralization of monoamine neurons: mesotelencephalic dopamine projections to caudate, septum, and frontal cortex. J Neurosci. 1981;1:1361–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Swanson LW. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull. 1982;9:321–53.

    CAS  PubMed  Google Scholar 

  11. Ford CP, Mark GP, Williams JT. Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location. J Neurosci. 2006;26:2788–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Margolis EB, Lock H, Chefer VI, Shippenberg TS, Hjelmstad GO, Fields HL. Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc Natl Acad Sci USA. 2006;103:2938–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL. Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition. J Neurosci. 2008;28:8908–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lammel S, Hetzel A, Hackel O, Jones I, Liss B, Roeper J. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron. 2008;57:760–73.

    CAS  PubMed  Google Scholar 

  15. Lammel S, Ion DI, Roeper J, Malenka RC. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron. 2011;70:855–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Beier KT, Steinberg EE, DeLoach KE, Xie S, Miyamichi K, Schwarz L, et al. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell. 2015;162:622–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Aragona BJ, Cleaveland NA, Stuber GD, Day JJ, Carelli RM, Wightman RM. Preferential enhancement of dopamine transmission within the nucleus accumbens shell by cocaine is attributable to a direct increase in phasic dopamine release events. J Neurosci. 2008;28:8821–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Aragona BJ, Day JJ, Roitman MF, Cleaveland NA, Wightman RM, Carelli RM. Regional specificity in the real-time development of phasic dopamine transmission patterns during acquisition of a cue-cocaine association in rats. Eur J Neurosci. 2009;30:1889–99.

    PubMed  PubMed Central  Google Scholar 

  19. Bassareo V, Musio P, Di, Chiara G. Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli. Psychopharmacology (Berl). 2011;214:687–97.

    CAS  PubMed  Google Scholar 

  20. Pontieri FE, Tanda G, Di Chiara G. Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc Natl Acad Sci USA. 1995;92:12304–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Bassareo V, De Luca MA, Di, Chiara G. Differential impact of pavlovian drug conditioned stimuli on In Vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex. Psychopharmacology (Berl). 2007;191:689–703.

    CAS  PubMed  Google Scholar 

  22. Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol. 2007;12:227–462.

    CAS  PubMed  Google Scholar 

  23. Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. 1993;18:247–91.

    CAS  PubMed  Google Scholar 

  24. Lipovsek M, Bardy C, Cadwell CR, Hadley K, Kobak D, Tripathy SJ. Patch-seq: past, present, and future. J Neurosci. 2021;41:937–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Cadwell CR, Palasantza A, Jiang X, Berens P, Deng Q, Yilmaz M, et al. Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq. Nat Biotechnol. 2016;34:199–203.

    CAS  PubMed  Google Scholar 

  26. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, et al. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science. 1998;282:1890–3.

    CAS  PubMed  Google Scholar 

  27. Jensen HS, Grunnet M, Olesen SP. Inactivation as a new regulatory mechanism for neuronal Kv7 channels. Biophys J. 2007;92:2747–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Soldovieri MV, Miceli F, Taglialatela M. Driving with no brakes: molecular pathophysiology of Kv7 potassium channels. Physiology (Bethesda). 2011;26:365–76.

    CAS  PubMed  Google Scholar 

  29. Jentsch TJ. Neuronal KCNQ potassium channels: physiology and role in disease. Nat Rev Neurosci. 2000;1:21–30.

    CAS  PubMed  Google Scholar 

  30. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996;12:17–23.

    PubMed  Google Scholar 

  31. Brueggemann LI, Cribbs LL, Byron KL. Heteromeric channels formed from alternating Kv7.4 and Kv7.5 alpha-subunits display biophysical, regulatory, and pharmacological characteristics of smooth muscle M-currents. Front Physiol. 2020;11:992.

    PubMed  PubMed Central  Google Scholar 

  32. Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell. 1999;96:437–46.

    CAS  PubMed  Google Scholar 

  33. Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ. KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem. 2000;275:24089–95.

    CAS  PubMed  Google Scholar 

  34. Schwake M, Pusch M, Kharkovets T, Jentsch TJ. Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J Biol Chem. 2000;275:13343–8.

    CAS  PubMed  Google Scholar 

  35. Zaika O, Hernandez CC, Bal M, Tolstykh GP, Shapiro MS. Determinants within the turret and pore-loop domains of KCNQ3 K+ channels governing functional activity. Biophys J. 2008;95:5121–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Schroeder BC, Kubisch C, Stein V, Jentsch TJ. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998;396:687–90.

    CAS  PubMed  Google Scholar 

  37. Carver CM, Shapiro MS. Gq-coupled muscarinic receptor enhancement of KCNQ2/3 channels and activation of TRPC channels in multimodal control of excitability in dentate gyrus granule cells. J Neurosci. 2019;39:1566–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Varghese N, Lauritano A, Taglialatela M, Tzingounis AV. KCNQ3 is the principal target of retigabine in CA1 and subicular excitatory neurons. J Neurophysiol. 2021;125:1440–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Hu H, Vervaeke K, Storm JF. M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region. J Neurosci. 2007;27:1853–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Yue C, Yaari Y. KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons. J Neurosci. 2004;24:4614–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hansen HH, Ebbesen C, Mathiesen C, Weikop P, Ronn LC, Waroux O, et al. The KCNQ channel opener retigabine inhibits the activity of mesencephalic dopaminergic systems of the rat. J Pharmacol Exp Ther. 2006;318:1006–19.

    CAS  PubMed  Google Scholar 

  42. Martire M, D’Amico M, Panza E, Miceli F, Viggiano D, Lavergata F, et al. Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes. J Neurochem. 2007;102:179–93.

    CAS  PubMed  Google Scholar 

  43. Li L, Sun H, Ding J, Niu C, Su M, Zhang L, et al. Selective targeting of M-type potassium K(v) 7.4 channels demonstrates their key role in the regulation of dopaminergic neuronal excitability and depression-like behaviour. Br J Pharmacol. 2017;174:4277–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Tan X, Liu X, Liu E, Liu M, Mu S, Hang Z, et al. Astrocyte-derived lactate/NADH alters methamphetamine-induced memory consolidation and retrieval by regulating neuronal synaptic plasticity in the dorsal hippocampus. Brain Struct Funct. 2022;227:2681–99.

    CAS  PubMed  Google Scholar 

  45. Tackenberg C, Ghori A, Brandt R. Thin, stubby or mushroom: spine pathology in Alzheimer’s disease. Curr Alzheimer Res. 2009;6:261–8.

    CAS  PubMed  Google Scholar 

  46. Wang Z, Jin T, Le Q, Liu C, Wang X, Wang F, et al. Retrieval-driven hippocampal NPTX2 plasticity facilitates the extinction of cocaine-associated context memory. Biol Psychiatry. 2020;87:979–91.

    CAS  PubMed  Google Scholar 

  47. Devienne G, Le Gac B, Piquet J, Cauli B. Single cell multiplex reverse transcription polymerase chain reaction after patch-clamp. J Vis Exp. 2018;136:57627.

  48. Xiao T, Wang Y, Wei H, Yu P, Jiang Y, Mao L. Electrochemical monitoring of propagative fluctuation of ascorbate in the live rat brain during spreading depolarization. Angew Chem Int Ed Engl. 2019;58:6616–9.

    CAS  PubMed  Google Scholar 

  49. Liu X, Xiao T, Wu F, Shen MY, Zhang M, Yu HH, et al. Ultrathin cell-membrane-mimic phosphorylcholine polymer film coating enables large improvements for In Vivo electrochemical detection. Angew Chem Int Ed Engl. 2017;56:11802–6.

    CAS  PubMed  Google Scholar 

  50. Groenewegen HJ, Wright CI, Beijer AV, Voorn P. Convergence and segregation of ventral striatal inputs and outputs. Ann N Y Acad Sci. 1999;877:49–63.

    CAS  PubMed  Google Scholar 

  51. Provence A, Malysz J, Petkov GV. The novel KV7.2/KV7.3 channel opener ICA-069673 reveals subtype-specific functional roles in guinea pig detrusor smooth muscle excitability and contractility. J Pharmacol Exp Ther. 2015;354:290–301.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang X, An H, Li J, Zhang Y, Liu Y, Jia Z, et al. Selective activation of vascular K(v) 7.4/K(v) 7.5 K(+) channels by fasudil contributes to its vasorelaxant effect. Br J Pharmacol. 2016;173:3480–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Knyazev GG. EEG delta oscillations as a correlate of basic homeostatic and motivational processes. Neurosci Biobehav Rev. 2012;36:677–95.

    PubMed  Google Scholar 

  54. Knyazev GG. Motivation, emotion, and their inhibitory control mirrored in brain oscillations. Neurosci Biobehav Rev. 2007;31:377–95.

    PubMed  Google Scholar 

  55. Stefanics G, Hangya B, Hernadi I, Winkler I, Lakatos P, Ulbert I. Phase entrainment of human delta oscillations can mediate the effects of expectation on reaction speed. J Neurosci. 2010;30:13578–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. van Wingerden M, Vinck M, Lankelma J, Pennartz CM. Theta-band phase locking of orbitofrontal neurons during reward expectancy. J Neurosci. 2010;30:7078–87.

    PubMed  PubMed Central  Google Scholar 

  57. Kaplan R, Bush D, Bonnefond M, Bandettini PA, Barnes GR, Doeller CF, et al. Medial prefrontal theta phase coupling during spatial memory retrieval. Hippocampus. 2014;24:656–65.

    PubMed  PubMed Central  Google Scholar 

  58. O’Neill PK, Gordon JA, Sigurdsson T. Theta oscillations in the medial prefrontal cortex are modulated by spatial working memory and synchronize with the hippocampus through its ventral subregion. J Neurosci. 2013;33:14211–24.

    PubMed  PubMed Central  Google Scholar 

  59. Cohen MX, Axmacher N, Lenartz D, Elger CE, Sturm V, Schlaepfer TE. Good vibrations: cross-frequency coupling in the human nucleus accumbens during reward processing. J Cogn Neurosci. 2009;21:875–89.

    PubMed  Google Scholar 

  60. Lega BC, Kahana MJ, Jaggi J, Baltuch GH, Zaghloul K. Neuronal and oscillatory activity during reward processing in the human ventral striatum. Neuroreport. 2011;22:795–800.

    PubMed  PubMed Central  Google Scholar 

  61. De Pascalis V, Varriale V, D’Antuono L. Event-related components of the punishment and reward sensitivity. Clin Neurophysiol. 2010;121:60–76.

    PubMed  Google Scholar 

  62. Montgomery SM, Buzsaki G. Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance. Proc Natl Acad Sci USA. 2007;104:14495–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Nyhus E, Curran T. Functional role of gamma and theta oscillations in episodic memory. Neurosci Biobehav Rev. 2010;34:1023–35.

    PubMed  PubMed Central  Google Scholar 

  64. Li Y, Pehrson AL, Waller JA, Dale E, Sanchez C, Gulinello M. A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)‘s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression. Front Neurosci. 2015;9:279.

    PubMed  PubMed Central  Google Scholar 

  65. Lv XF, Xu Y, Han JS, Cui CL. Expression of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) in the nucleus accumbens is critical for the acquisition, expression and reinstatement of morphine-induced conditioned place preference. Behav Brain Res. 2011;223:182–91.

    CAS  PubMed  Google Scholar 

  66. Mabb AM, Ehlers MD. Arc ubiquitination in synaptic plasticity. Semin Cell Dev Biol. 2018;77:10–6.

    CAS  PubMed  Google Scholar 

  67. Berridge KC, Robinson TE. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev. 1998;28:309–69.

    CAS  PubMed  Google Scholar 

  68. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8:1481–9.

    CAS  PubMed  Google Scholar 

  69. Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci. 2006;29:565–98.

    CAS  PubMed  Google Scholar 

  70. Salamone JD, Correa M, Farrar A, Mingote SM. Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology (Berl). 2007;191:461–82.

    CAS  PubMed  Google Scholar 

  71. Koyama S, Appel SB. Characterization of M-current in ventral tegmental area dopamine neurons. J Neurophysiol. 2006;96:535–43.

    CAS  PubMed  Google Scholar 

  72. Hadley JK, Noda M, Selyanko AA, Wood IC, Abogadie FC, Brown DA. Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels. Br J Pharmacol. 2000;129:413–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhao C, Su M, Wang Y, Li X, Zhang Y, Du X, et al. Selective Modulation of K(+) Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons. Front Cell Neurosci. 2017;11:405.

    PubMed  PubMed Central  Google Scholar 

  74. Friedman AK, Juarez B, Ku SM, Zhang H, Calizo RC, Walsh JJ, et al. KCNQ channel openers reverse depressive symptoms via an active resilience mechanism. Nat Commun. 2016;7:11671.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. McNamara CG, Tejero-Cantero A, Trouche S, Campo-Urriza N, Dupret D. Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence. Nat Neurosci. 2014;17:1658–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Hipp JF, Hawellek DJ, Corbetta M, Siegel M, Engel AK. Large-scale cortical correlation structure of spontaneous oscillatory activity. Nat Neurosci. 2012;15:884–90.

    CAS  PubMed  Google Scholar 

  77. Marrion NV. Control of M-current. Annu Rev Physiol. 1997;59:483–504.

    CAS  PubMed  Google Scholar 

  78. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci. 2007;8:844–58.

    CAS  PubMed  Google Scholar 

  79. Stuber GD, Klanker M, de Ridder B, Bowers MS, Joosten RN, Feenstra MG, et al. Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons. Science. 2008;321:1690–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Luscher C, Malenka RC. Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron. 2011;69:650–63.

    PubMed  PubMed Central  Google Scholar 

  81. Saal D, Dong Y, Bonci A, Malenka RC. Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron. 2003;37:577–82.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Translational Medicine Core Facility of Shandong University for consultation and instrument availability that supported this work.

Funding

This study was supported by the National Natural Science Foundation of China, Grant Number: U220011 and 81871044.

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Shandong University School of Basic Medicine, Jinan, Shandong, China

    E Liu, Kunkun Pang, Min Liu, Xu Tan, Zhaofang Hang, Shouhong Mu, Weikai Han, Qingwei Yue & Jinhao Sun

  2. Department of Ultrasound, The Second Hospital of Shandong University, Jinan, Shandong, China

    Kunkun Pang

  3. Department of Psychiatry, McGill University, Montréal, QC, Canada

    Stefano Comai

  4. Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy

    Stefano Comai

  5. Department of Biomedical Sciences, University of Padua, Padua, Italy

    Stefano Comai

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Contributions

JS and EL designed this experiment and prepared the manuscript. EL also performed experiments and wrote the draft. KP, ML, XT, RS, ZH, SM and WH participated in some of the experiments and analyzed the data. SC provided critical revision for important intellectual content and revised the manuscript draft. All authors reviewed and approved the manuscript.

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Liu, E., Pang, K., Liu, M. et al. Activation of Kv7 channels normalizes hyperactivity of the VTA-NAcLat circuit and attenuates methamphetamine-induced conditioned place preference and sensitization in mice. Mol Psychiatry 28, 5183–5194 (2023). https://doi.org/10.1038/s41380-023-02218-5

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