Abstract
Drug addiction is characterized by relapse when addicts are re-exposed to drug-associated environmental cues, but the neural mechanisms underlying cue-induced relapse are unclear. In the present study we investigated the role of a specific dopaminergic (DA) pathway from ventral tegmental area (VTA) to nucleus accumbens core (NAcore) in mouse cue-induced relapse. Optical intracranial self-stimulation (oICSS) was established in DAT-Cre transgenic mice. We showed that optogenetic excitation of DA neurons in the VTA or their projection terminals in NAcore, NAshell or infralimbic prefrontal cortex (PFC-IL) was rewarding. Furthermore, activation of the VTA-NAcore pathway alone was sufficient and necessary to induce reinstatement of oICSS. In cocaine self-administration model, cocaine-associated cues activated VTA DA neurons as assessed by intracellular GCaMP signals. Cue-induced reinstatement of cocaine-seeking was triggered by optogenetic stimulation of the VTA-NAcore pathway, and inhibited by chemogenetic inhibition of this pathway. Together, these results demonstrate that cue-induced reinstatement of reward seeking is in part mediated by activation of the VTA-NAcore DA pathway.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81573405 and U1502225), Natural Science Foundation of Beijing (7212159), National Key R&D Program of China (2016YFC0800907), National Key R&D Program of China (2017YFC131040), Medical Innovation Program (16CXZ033) and Beijing Nova Program (xx2014A014).
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RS, NW and JL initiated this project. RS designed the study. TYZ and XH bred the mice. MYJ and XYD conducted the experiments and analyzed the data. MML provided technical support. MYJ and RS wrote and revised the manuscript.
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Jing, My., Ding, Xy., Han, X. et al. Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice. Acta Pharmacol Sin 43, 2276–2288 (2022). https://doi.org/10.1038/s41401-022-00866-x
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DOI: https://doi.org/10.1038/s41401-022-00866-x
