Adelie Salin

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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.