scholarly journals Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking

2009 ◽  
Vol 30 (5) ◽  
pp. 889-900 ◽  
Author(s):  
Rita A. Fuchs ◽  
Guinevere H. Bell ◽  
Donna R. Ramirez ◽  
Jessica L. Eaddy ◽  
Zu-In Su
Keyword(s):  
Basolateral Amygdala ◽  
Memory Reconsolidation ◽  
Cocaine Seeking

scholarly journals CB1 receptor signaling modulates amygdalar plasticity during context-cocaine memory reconsolidation to promote subsequent cocaine seeking

2020 ◽  
Author(s):  
Jessica A. Higginbotham ◽  
Rong Wang ◽  
Ben D. Richardson ◽  
Hiroko Shiina ◽  
Shi Min Tan ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Early Gene ◽  
Memory Reconsolidation ◽  
Associative Memories ◽  
Potential Therapeutic Target ◽  
Cannabinoid Type 1 Receptor ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
With Memory

ABSTRACTContextual drug-associated memories precipitate craving and relapse in cocaine users. Such associative memories can be weakened through interference with memory reconsolidation, a process by which memories are maintained following memory retrieval-induced destabilization. We hypothesized that cocaine-memory reconsolidation requires cannabinoid type 1 receptor (CB1R) signaling based on the fundamental role of the endocannabinoid system in synaptic plasticity and emotional memory processing. Using an instrumental rat model of cocaine relapse, we evaluated whether systemic CB1R antagonism (AM251; 3 mg/kg, I.P.) during memory reconsolidation alters (a) subsequent drug context-induced cocaine-seeking behavior, as well as (b) cellular adaptations and (c) excitatory synaptic physiology in the basolateral amygdala (BLA). Systemic CB1R antagonism – during, but not after, cocaine-memory reconsolidation – reduced drug context-induced cocaine-seeking behavior three days, but not three weeks, later. CB1R antagonism also inhibited memory retrieval-associated increases in BLA zinc finger 268 (zif268) and activity regulated cytoskeletal-associated protein (Arc) immediate-early gene expression and changes in BLA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) subunit phosphorylation that likely contribute to increased receptor membrane trafficking and synaptic plasticity during memory reconsolidation. Furthermore, CB1R antagonism increased memory reconsolidation-associated spontaneous excitatory post-synaptic current frequency in BLA principal neurons during memory reconsolidation. Together, these findings suggest that CB1R signaling modulates cellular and synaptic mechanisms in the BLA during cocaine-memory reconsolidation, thereby facilitating cocaine-memory maintenance. These findings identify the CB1R as a potential therapeutic target for relapse prevention.SIGNIFICANCE STATEMENTDrug relapse can be triggered by the retrieval of context-drug memories upon re-exposure to a drug-associated environment. Context-drug associative memories become destabilized upon retrieval and must be reconsolidated into long-term memory stores in order to persist. Hence, targeted interference with memory reconsolidation can weaken maladaptive context-drug memories and reduce the propensity for drug relapse. Our findings indicate that cannabinoid type 1 receptor (CB1R) signaling is critical for context-cocaine memory reconsolidation and subsequent drug context-induced reinstatement of cocaine-seeking behavior. Furthermore, cocaine-memory reconsolidation is associated with CB1R-dependent immediate-early gene expression and changes in excitatory synaptic proteins and physiology in the basolateral amygdala. Together, our findings provide initial support for CB1R as a potential therapeutic target for relapse prevention.

scholarly journals Basolateral amygdala CB1 receptors modulate HPA axis activation and context-cocaine memory strength during reconsolidation

2020 ◽  
Author(s):  
Jessica A. Higginbotham ◽  
Nicole M. Jones ◽  
Rong Wang ◽  
Ryan J. McLaughlin ◽  
Rita A. Fuchs
Keyword(s):  
Memory Retrieval ◽  
Basolateral Amygdala ◽  
Memory Reconsolidation ◽  
Long Term Memory ◽  
Memory Strength ◽  
Corticosterone Concentration ◽  
Cannabinoid Type 1 Receptor ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
The Impact

ABSTRACTRe-exposure to a cocaine-associated context triggers craving and relapse through the retrieval of salient context-drug memories. Upon retrieval, context-drug memories become labile and temporarily sensitive to modification before they are reconsolidated into long-term memory stores. Cannabinoid type 1 receptor (CB1R) signaling is necessary for cocaine-memory reconsolidation and associated glutamatergic plasticity in the basolateral amygdala (BLA); however, it remains unclear whether CB1Rs in the BLA mediate this phenomenon. To investigate this question, we examined whether CB1R antagonist or agonist administration into the BLA immediately after cocaine-memory retrieval (i.e., during memory reconsolidation) alters cocaine-memory strength and subsequent drug context-induced cocaine-seeking behavior in an instrumental rodent model of cocaine relapse. Intra-BLA administration of the CB1R antagonist, AM251 (0.3 µg/hemisphere) – during, but not after, memory reconsolidation – increased drug context-induced cocaine-seeking behavior three days later, while the CB1R agonist, WIN55,212-2 (0.5 µg/hemisphere) failed to alter this behavior. Furthermore, AM251 administration into the posterior caudate putamen (anatomical control region) during memory reconsolidation did not alter subsequent context-induced cocaine-seeking behavior. In a follow-up experiment, cocaine-memory retrieval elicited robust hypothalamic-pituitary-adrenal axis activation, as indicated by an increase in blood serum corticosterone concentration, and this response was selectively extended by intra-BLA AM251 administration during the putative time of memory reconsolidation relative to all control conditions. Together, these findings suggest that CB1R populations in the BLA gate memory strength or interfere with memory maintenance, possibly by diminishing the impact of cue-induced arousal on the integrity of the reconsolidating memory trace or on the efficiency of the memory reconsolidation process.

scholarly journals Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

2019 ◽  
Author(s):  
Koral Goltseker ◽  
Hen Handrus ◽  
Segev Barak
Keyword(s):  
Memory Retrieval ◽  
Lever Press ◽  
Water Flooding ◽  
Memory Reconsolidation ◽  
Place Conditioning ◽  
Self Administration ◽  
Conditioning Paradigm ◽  
Cocaine Seeking ◽  
Lever Pressing ◽  
Alcohol Seeking

AbstractRelapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a “reconsolidation” process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addiction-related behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol-memory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after alcohol-memory retrieval. Furthermore, rats trained to lever-press for alcohol showed decreased context-induced renewal of alcohol-seeking responding when the lever-pressing was counterconditioned with foot-shocks, shortly, but not 6 h, after memory retrieval. These results 0suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol-memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Also, we found that aversive counterconditioning preceded by alcohol-memory retrieval was characterized by upregulation of brain-derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that Bdnf plays a role in the memory updating process.

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