Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

Post-traumatic stress disorder (PTSD) is a psychiatric disorder caused by traumatic past experiences, rooted in the neurocircuits of fear memory formation. Memory processes include encoding, storing, and recalling to forgetting, suggesting the potential to erase fear memories through timely interventions. Conventional strategies such as medications or electroconvulsive therapy often fail to provide permanent relief and come with significant side-effects. This review explores how fear memory may be erased, particularly focusing on the mnemonic phases of reconsolidation and extinction. Reconsolidation strengthens memory, while extinction weakens it. Interfering with memory reconsolidation could diminish the fear response. Alternatively, the extinction of acquired memory could reduce the fear memory response. This review summarizes experimental animal models of PTSD, examines the nature and epidemiology of reconsolidation to extinction, and discusses current behavioral therapy aimed at transforming fear memories to treat PTSD. In sum, understanding how fear memory updates holds significant promise for PTSD treatment.
Fear/psychology* ; Extinction, Psychological/physiology* ; Animals ; Stress Disorders, Post-Traumatic/psychology* ; Humans ; Memory Consolidation/physiology* ; Memory/physiology*

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Animals ; Brain ; physiology ; Extinction, Psychological ; physiology ; Humans ; Long-Term Potentiation ; Long-Term Synaptic Depression ; Neural Pathways ; physiology ; Neuronal Plasticity ; Neurons ; physiology ; Receptors, AMPA ; physiology

OBJECTIVETo investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior.

METHODSSD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system.

RESULTSIn rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period.

CONCLUSIONMorphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

Animals ; Cerebral Cortex ; drug effects ; physiology ; Drug-Seeking Behavior ; physiology ; Electrophysiological Phenomena ; Extinction, Psychological ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Telemetry

Animals ; Conditioning (Psychology) ; drug effects ; Extinction, Psychological ; drug effects ; physiology ; Fear ; drug effects ; physiology ; Male ; Mifepristone ; pharmacology ; Rats ; Rats, Sprague-Dawley

Animals ; Extinction, Psychological ; physiology ; Fear ; physiology ; Male ; Mental Recall ; physiology ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation ; complications ; physiopathology ; Sleep, REM ; physiology

Animals ; Avoidance Learning ; physiology ; Cues ; Extinction, Psychological ; physiology ; Fear ; physiology ; Male ; Mental Recall ; physiology ; Rats ; Sleep Deprivation ; physiopathology ; Sleep, REM ; physiology