Inhibition of protein synthesis but not β-adrenergic receptors blocks reconsolidation of a cocaine-associated cue memory

Abstract

Previously consolidated memories have the potential to enter a state of lability upon memory recall, during which time the memory can be altered before undergoing an additional consolidation-like process and being stored again as a longterm memory. Blocking reconsolidation of aberrant memories has been proposed as a potential treatment for psychiatric disorders including addiction. Here we investigated of the effect of systemically administering the protein synthesis inhibitor cycloheximide or the b-adrenergic antagonist propranolol on reconsolidation. Rats were trained to self-administer cocaine, during which each lever press resulted in the presentation of a cue paired with an intravenous infusion of cocaine. After undergoing lever press extinction to reduce operant responding, the cue memory was reactivated and rats were administered systemic injections of propranolol, cycloheximide, or vehicle. Post-reactivation cycloheximide, but not propranolol, resulted in a reactivation-dependent decrease in cue-induced reinstatement, indicative of reconsolidation blockade by protein synthesis inhibition. The present data indicate that systemically targeting protein synthesis as opposed to the b-adrenergic system may more effectively attenuate the reconsolidation of a drug-related memory and decrease drug-seeking behavior.

Garcinol Blocks the Reconsolidation of Multiple Cocaine-Paired Cues after a Single Cocaine-Reactivation Session

“…Most clinical studies of reconsolidation and substance use in the literature have investigated the β-adrenergic antagonist propranolol with mixed results (Jobes et al, 2015;Lonergan et al, 2016;Pachas et al, 2015;Saladin et al, 2013;Zhao et al, 2011). However, preclinical investigations of garcinol and propranolol in a CS-reactivation paradigm have demonstrated that garcinol may be more effective at reducing reinstatement than propranolol (Dunbar and Taylor, 2016). Similar results were found with propranolol in a USreactivation paradigm in our lab (unpublished preliminary data).…”

Modulating reconsolidation and extinction to regulate drug reward memory

“…In alcohol‐related studies, it was shown that post‐retrieval injection of propranolol did not affect alcohol‐induced CPP, but did reduce alcohol‐seeking behavior and disrupt the ability of alcohol‐associated cue to act as a conditioned reinforcer, suggesting that the effects of propranolol may be task‐dependent in alcohol dependence (Wouda et al ., ; Font & Cunningham, ; Schramm et al ., ). Interesting, conflicting results from the cocaine SA model were reported such that propranolol either disrupted (Milton et al ., ) or did not affect cocaine reward memory (Dunbar & Taylor, ). A recent study demonstrated that β1‐adrenergic receptor/β‐arrestin 2/ERK‐biased signaling is involved in the reconsolidation of cocaine reward memory (Liu et al ., ).…”

Reconsolidation and psychopathology: Moving towards reconsolidation-based treatments

“…Specifically, propranolol may be more effective at inhibiting aberrant aversive memories in disorders such as PTSD as opposed to aberrant reward-related memories in disorders such as substance use. This idea is supported by our preclinical findings that systemically administered propranolol does not impair the reconsolidation of cocaine-cue memories in a model of reinstatement (i.e., relapse) to cocaine-seeking behavior in rodents trained to self-administer cocaine (Dunbar and Taylor 2016). …”