The amygdala–ventral pallidum pathway contributes to a hypodopaminergic state in the ventral tegmental area during protracted abstinence from chronic cocaine

Autor: Adélie Salin, Emilie Dugast, Virginie Lardeux, Marcello Solinas, Pauline Belujon
Přispěvatelé: Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work was supported by the Institute National de la Santé et de la Recherche Médicale, the Centre National pour la Recherche Scientifique, the University of Poitiers, CHU of Poitiers, SFR FED 4226and the Agence Nationale de la Recherche (ANR JC, ANR-15-CE37-0010 to P.B.)., ANR-15-CE37-0010,PlastCocIC,Rôle du circuit amygdale-cortex insulaire dans le risque persistant de rechute(2015)
Rok vydání: 2023
Předmět:
Zdroj: British Journal of Pharmacology
British Journal of Pharmacology, 2023, ⟨10.1111/bph.16034⟩
ISSN: 1476-5381
0007-1188
Popis: International audience; BACKGROUND AND PURPOSE: Incubation of craving, the progressive increase in drug seeking over the first weeks of abstinence, is associated with temporal changes during abstinence in the activity of several structures involved in drug-seeking behavior. Decrease of dopamine (DA) release and decrease in DA neurons’ activity (hypodopaminergic state) have been reported in the ventral tegmental area (VTA) during cocaine abstinence but the mechanisms underlying these neuroadaptations are not well understood. Here, we investigated the potential involvement of a VTA inhibiting circuit (basolateral amygdala (BLA)-ventral pallidum (VP) pathway) in the hypodopaminergic state associated with abstinence from chronic cocaine. EXPERIMENTAL APPROACH: In a model of cocaine self-administration, we performed in vivo electrophysiological recordings of DA VTA neurons and 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 significant decreases in VTA DA population activity and significant increases in BLA activity after protracted but not after short-term abstinence from chronic cocaine. The decrease in VTA DA activity was restored by pharmacological inhibition of the activity of either the BLA or the VP, suggesting that these regions exert a negative influence on DA activity. CONCLUSION AND IMPLICATIONS: Our study sheds new lights on neuroadaptations occurring during incubation of craving leading to relapse. In particular, we describe the involvement of the BLA-VP pathway in cocaine-induced decreases of DA activity in the VTA. This study adds important information about the specific brain network dysfunctions underlying hypodopaminergic activity during abstinence.
Databáze: OpenAIRE
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