Reconsolidation of a cocaine-associated stimulus requires amygdalar protein kinase A

Drug addiction is a chronic disorder associated with recurrent craving and relapse often precipitated by the presence of drug-associated stimuli. Pharmacological and behavioral treatments that disrupt drug-associated stimulus memories could be beneficial in the treatment of addictive disorders. Memory restabilization (or reconsolidation) following retrieval of drug-paired stimuli depends upon the amygdala. Here we assessed whether amygdalar PKA is required for the reconsolidation of an appetitive, cocaine-paired stimulus. Rats were trained to lever press for intravenous cocaine infusions paired with a light/tone conditioned stimulus. After 12 d of acquisition, rats either underwent lever extinction (8-12 d) followed by light/tone reactivation and subsequent cue-induced and cocaine-induced (15 mg/kg, i.p.) reinstatement testing or were subsequently tested to assess the ability of the light/tone stimulus to serve as a conditioned reinforcer in the acquisition of a new instrumental response (nose poking). Bilateral intra-amygdalar infusions of the PKA inhibitor Rp-cAMPS (18 microg per side) given immediately following light/tone stimulus reactivation decreased subsequent cue-induced reinstatement and responding with a conditioned reinforcer, while having no effect on cocaine-induced reinstatement. Intra-amygdalar infusions of Rp-cAMPS made 3 h following reactivation or immediately following no stimulus reactivation had no effect on subsequent cue-induced reinstatement. These data show that memory reconsolidation for a cocaine-paired stimulus is retrieval dependent and time limited and critically depends upon amygdalar PKA.