GABAB receptor modulation during drug-memory reconsolidation: current evidence and translational priorities for relapse prevention

Relapse after abstinence is sustained in part by drug-associated memories reactivated by cues, contexts, actions, and interoceptive states. Reconsolidation-based interventions seek to modify a retrieved memory during transient lability. GABA B receptors suppress transmitter release, hyperpolarize neurons, and inhibit adenylyl-cyclase-cAMP-protein-kinase-A signaling, providing biological plausibility for temporally aligned modulation. This structured narrative review organizes the literature using a non-comparative evidence-domain framework. Direct retrieval-window evidence remains limited to two local baclofen studies in male mice using morphine conditioned place preference; both reported retrieval dependence, but only the agranular insular cortex study included a delayed-treatment comparison. Earlier systemic baclofen studies conducted during repeated extinction and post-conditioning GABA B positive allosteric modulator studies support memory-related pharmacology but do not isolate a retrieval window. A systemic post-reactivation baclofen study extends the evidence beyond local microinjection, whereas human baclofen and ASP8062 studies define tolerability, exposure, CNS pharmacodynamics, and non-timed clinical boundaries rather than reconsolidation efficacy. Translation requires a validated reactivation procedure, adequate pharmacokinetic coverage and CNS pharmacodynamic engagement, randomized retrieval and timing controls, post-acute persistence, and protection against sedation, task disengagement, and repeated-cue confounding. The evidence supports a falsifiable development hypothesis, not memory erasure or a universal anti-addiction therapy.