Preventing incubation of drug craving to treat drug relapse: from bench to bedside

Liu, Xiaoxing; Yuan, Kai; Lu, Tangsheng; Lin, Xiao; Zheng, Wei; Xue, Yan-Xue; Shi, Jie; Lü, Lin; Han, Ying

doi:10.1038/s41380-023-01942-2

Cited by 13 publications

(6 citation statements)

References 145 publications

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“…Notably, a similar phenomenon has been reported in previous ndings that cue-induced drug craving (i.e., an intense desire for the effects of a drug) progressively increased during long-term abstinence, which was termed as the incubation of cue-induced drug craving 31,32 . The incubated drug craving is a critical contributor to drug relapse and generalizes across various drugs 33 . Many human studies have identi ed this phenomenon in individuals with a history of taking nicotine 34 , methamphetamine 35 , alcohol 36 , or cocaine 37 .…”

Section: Discussionmentioning

confidence: 99%

Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit

Liu,

Lu,

Chen

et al. 2024

Mol Psychiatry

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Remote memory usually decreases over time, whereas remote drug-cue associated memory exhibits enhancement, increasing the risk of relapse during abstinence. Memory system consolidation is a prerequisite for remote memory formation, but neurobiological underpinnings of the role of consolidation in the enhancement of remote drug memory are unclear. Here, we found that remote cocaine-cue associated memory was enhanced in rats that underwent self-administration training, together with a progressive increase in the response of prelimbic cortex (PrL) CaMK neurons to cues. System consolidation was required for the enhancement of remote cocaine memory through PrL CaMK neurons during the early period post-training. Furthermore, dendritic spine maturation in the PrL relied on the basolateral amygdala (BLA) input during the early period of consolidation, contributing to remote memory enhancement. These ndings indicate that memory consolidation drives the enhancement of remote cocaine memory through a time-dependently increase in activity and maturation of PrL CaMK neurons receiving a sustained BLA input.

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Section: Discussionmentioning

confidence: 99%

Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit

Liu,

Lu,

Chen

et al. 2024

Mol Psychiatry

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“…Moreover, neural mechanisms between animals and humans are not similar. There is uncertainty about the effect and efficiency of the same intervention from animals to humans ( 63 ). Last, our animal study suggested CeA as a potential brain region for medication intervention.…”

Section: Discussionmentioning

confidence: 99%

Disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawal

Chen,

Zhang,

Liang

et al. 2023

Sci. Adv.

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Energy supply, especially the transfer of lactate from astrocytes to neurons, is critical for neuronal plasticity. However, its role in the incubation of cocaine craving remains largely unknown. Using an extended-access self-administration model and in vivo 1 H-magnetic resonance spectroscopy, we found that lactate synthesis in the central amygdala (CeA) is required for the intensified cocaine craving after prolonged withdrawal. Furthermore, incubated cocaine seeking was associated with a selective increase in monocarboxylate transporter 2 (MCT2) and MCT4 expression levels. Down-regulation of astrocytic MCT4 or neuronal MCT2 using targeted antisense oligonucleotides or cell type–specific shRNA attenuated cocaine craving and reduced the expression of plasticity-related proteins and excitatory synaptic transmission. Meanwhile, lactate administration rescued MCT4 but not MCT2 disruption–induced behavioral changes due to the inability of lactate to be transported into neurons. Together, our study highlights the critical role of astrocyte-neuron lactate transport in the CeA in the incubation of cocaine craving and suggests a potential therapeutic target for drug addiction.

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“…In these models, craving reliably displays an inverted U-shaped relationship across time, such that it is highest at moderate stages of abstinence (Shalev et al, 2001, Grimm et al, 2003). While these animal models have provided a foundation for understanding the mechanisms of craving and relapse (Pickens et al, 2011, Loweth et al, 2014, Dong et al, 2017, Reiner et al, 2019, Altshuler et al, 2020, Venniro et al, 2021), the translational value of rodent models into humans has been limited based on differences in how craving is probed across species (Liu et al, 2023).…”

Section: Figurementioning

confidence: 99%

“…Human studies of incubation have mainly relied on self-report measures of craving which represent hedonic feelings toward the prospect of reward rather than motivational vigor evoked by the drug (Nava et al, 2008, Bedi et al, 2011, Wang et al, 2013, Parvaz et al, 2016, Li et al, 2016) or food cues (Coutinho et al, 2018). In animal models, craving is typically queried by lever presses reinforced by cues previously associated with reward, which is thought to more directly represent motivational vigor (Liu et al, 2023). This contrast creates a disconnect within the literature where animal models of incubation assess craving by measuring the behaviors animals perform to seek rewards and human models measure the associated feelings.…”

Section: Figurementioning

confidence: 99%

Connecting self-report and instrumental behavior during incubation of food craving in humans

Ruiz,

Eckardt,

Briand

et al. 2023

Preprint

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Incubation of craving is a phenomenon describing the intensification of craving for a reward over extended periods of abstinence from reinforcement. Animal models employ instrumental markers of craving to reward cues to examine incubation, while homologous human paradigms often rely on subjective self-reports. Here, we characterize a novel human paradigm that showed strong positive relationships between self-reports and instrumental markers of craving. Further, both measures expressed non-linear relationships with time since last consumption, which parallels homologous animal paradigms of incubation of craving.

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Preventing incubation of drug craving to treat drug relapse: from bench to bedside

Cited by 13 publications

References 145 publications

Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit

Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit

Disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawal

Connecting self-report and instrumental behavior during incubation of food craving in humans

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