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Publication : An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

First Author  Tian G Year  2022
Journal  Cell Rep Volume  39
Issue  5 Pages  110775
PubMed ID  35508124 Mgi Jnum  J:325098
Mgi Id  MGI:7283981 Doi  10.1016/j.celrep.2022.110775
Citation  Tian G, et al. (2022) An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement. Cell Rep 39(5):110775
abstractText  Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTA(DA)-->amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTA(DA)-->amygdala cells that can be detected even after a single cocaine exposure. Activity in BNST(GABA)-->midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTA(DA)-->amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.
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