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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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Titel: The amygdala-ventral pallidum pathway contributes to a hypodopaminergic state in the ventral tegmental area during protracted abstinence from chronic cocaine
Autoren: Salin, Adélie, Dugast, Emilie, Lardeux, Virginie, Solinas, Marcello, Belujon, Pauline
Weitere Verfasser: Jonchère, Laurent, Laboratoire de neurosciences expérimentales et cliniques U 1084 (LNEC Poitiers ), Université de Poitiers = University of Poitiers (UP)-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), Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ), 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)
Quelle: British Journal of Pharmacology. 180:1819-1831
Verlagsinformationen: Wiley, 2022.
Publikationsjahr: 2022
Schlagwörter: 0301 basic medicine, MESH: Rats, Basal Forebrain, MESH: Basal Forebrain* / metabolism, [SDV]Life Sciences [q-bio], Dopamine, cocaine, incubation of craving, MESH: Amygdala / metabolism, ventral pallidum, MESH: Ventral Tegmental Area / metabolism, Rats, Sprague-Dawley, 03 medical and health sciences, Cocaine, MESH: Dopaminergic Neurons / metabolism, Animals, MESH: Animals, dysphoria, relapse, 0303 health sciences, Dopaminergic Neurons, Ventral Tegmental Area, amygdala, Amygdala, MESH: Cocaine* / pharmacology, Rats, [SDV] Life Sciences [q-bio], MESH: Dopamine / metabolism, Sprague-Dawley, dopamine
Beschreibung: 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.
Publikationsart: Article
Dateibeschreibung: application/pdf
ISSN: 1476-5381
0007-1188
DOI: 10.22541/au.166266560.09303461/v1
DOI: 10.1111/bph.16034
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/36645812
https://hal.science/hal-03971992v1
https://hal.science/hal-03971992v1/document
https://doi.org/10.1111/bph.16034
Rights: CC BY
Dokumentencode: edsair.doi.dedup.....7feded083628df0ac68c5f5e7aba09bf
Datenbank: OpenAIRE
Beschreibung
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.
ISSN:14765381
00071188
DOI:10.22541/au.166266560.09303461/v1