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

Authors

Kuisheng Sun, Li Deng, Tao Li, Wenhua Huang, Wanli Lin

Published in

Frontiers in pharmacology. Volume 17. Pages 1944369. Epub Sep 23, 2026.

Abstract

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.

PMID:
42846061
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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