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