Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior

Drug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending on the basolateral amygdala (BLA). Pharmacology or behavior treatment that disrupts the reconsolidation can effectively attenuate drug-seeking in addicts. Here, we hypothesized that heroin-memory reconsolidation requires cAMP-dependent protein kinase A (PKA) of BLA based on the fundamental effect of PKA in synaptic plasticity and memory process. After 10 days of acquisition, the rats underwent 11 days of extinction training and then received the intra-BLA infusions of the PKA inhibitor Rp-cAMPS at different time windows with/without a reactivation session. The results show that PKA inhibitor treatment in the reconsolidation time window disrupts the reconsolidation and consequently reduces cue-induced reinstatement, heroin-induced reinstatement, and spontaneous recovery of heroin-seeking behavior in the rats. In contrast, there was no effect on cue-induced reinstatement in the intra-BLA infusion of PKA inhibitor 6 h after reactivation or without reactivation. These data suggest that PKA inhibition disrupts the reconsolidation of heroin-associated memory, reduces subsequent drug seeking, and prevents relapse, which is retrieval-dependent, time-limited, and BLA-dependent.