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The amygdala-ventral pallidum pathway contributes to a hypodopaminergic state in the ventral tegmental area during protracted abstinence from chronic cocaine
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  • Adelie Salin,
  • Emilie Dugast,
  • Virginie Lardeux,
  • Marcello Solinas,
  • Pauline Belujon
Adelie Salin
University of Poitiers

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Emilie Dugast
University of Poitiers
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Virginie Lardeux
University of Poitiers
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Marcello Solinas
University of Poitiers
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Pauline Belujon
University of Poitiers
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Abstract

Background and Purpose Incubation of craving is associated with temporal changes in the activity of several structures involved in drug-seeking behavior. Hypodopaminergic activity, responsible for negative emotional states, has been reported in the ventral tegmental area (VTA) during cocaine abstinence. The neuroadaptations underlying the VTA hyperdopaminergic state after chronic cocaine is not well understood. In this work, we investigated the potential involvement of a VTA inhibiting circuit (amygdala-ventral pallidum (VP) pathway) in the hypodopaminergic state during abstinence from chronic cocaine. Experimental Approach In a model of cocaine self-administration, we performed in vivo electrophysiological recordings of DA VTA neurons and basolateral amygdala (BLA) neurons from anesthetized rats during early and protracted abstinence and evaluated the involvement of the BLA-VP pathway using a pharmacological approach. Key Results We found a significant decrease of VTA DA population activity and a significant increase of BLA activity after 30 days of abstinence from chronic cocaine but not one day. The decrease in VTA DA activity was restored by pharmacological inhibition of the activity of either the BLA or the VP. Conclusion and Implications Our study sheds new lights on neuroadaptations occurring during incubation of craving leading to relapse. In particular, we described the involvement of the BLA-VP pathway in cocaine-induced decreases of DA activity in the VTA. This study adds an important building block to the characterization of specific brain network dysfunctions underlying hypodopaminergic activity during abstinence.
06 Sep 2022Submitted to British Journal of Pharmacology
08 Sep 2022Submission Checks Completed
08 Sep 2022Assigned to Editor
18 Sep 2022Reviewer(s) Assigned
09 Nov 2022Review(s) Completed, Editorial Evaluation Pending
10 Nov 2022Editorial Decision: Revise Minor
30 Nov 20221st Revision Received
02 Dec 2022Submission Checks Completed
02 Dec 2022Assigned to Editor
02 Dec 2022Review(s) Completed, Editorial Evaluation Pending
06 Dec 2022Reviewer(s) Assigned
06 Jan 2023Editorial Decision: Accept