# Context-induced Cocaine Relapse: Influence of Cocaine Memory Reconsolidation

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $378,026

## Abstract

PROJECT SUMMARY/ABSTRACT
Intractable cocaine craving precipitated by exposure to a cocaine-associated environmental context is a major
factor contributing to drug relapse. This phenomenon depends on available long-term memories of context-
response-drug associations. Recent findings indicate that associative memories become labile upon retrieval
and need to undergo protein synthesis-dependent reconsolidation into long-term memory stores in order to be
retained over time. Cocaine-induced pathology in memory reconsolidation may result in unusually salient or
intrusive cocaine memories that manifest as increased cue reactivity and propensity for drug relapse in a drug-
associated environment. Thus, the long-term goal of this research program is to enhance our understanding of
the functional neuroanatomy and cellular mechanisms of cocaine memory reconsolidation. During the previous
funding period, we have shown that protein synthesis-dependent memory reconsolidation occurs in the
basolateral amygdala. Remarkably, this process is functionally dependent on neural activity in the dorsal
hippocampus, even though the two brain regions do not share monosynaptic connections. Logically extending
this line of research in this competitive renewal application, Specific Aim 1 will identify novel memory
reconsolidation circuits. Based on our new preliminary findings, we will test the hypothesis that the locus
coeruleus serves as a relay between the dorsal hippocampus and basolateral amygdala to permit cocaine
memory reconsolidation. In addition, we will evaluate how the inhibition of specific pathways within this putative
circuitry alters electrophysiological activity at the targeted terminal region of each pathway. During the previous
funding period, we also identified cellular mechanisms that are necessary for cocaine memory reconsolidation.
Systematically extending this line of research, Specific Aim 2 will identify novel cellular mechanisms of cocaine
memory reconsolidation in the basolateral amygdala. Based on our preliminary findings, Aim 2 will focus on the
endocannabinoids (eCB), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in the basolateral amygdala.
We will evaluate the extent to which memory reconsolidation is sufficient to produce changes in eCB levels, eCB
degradation, and pyramidal cell excitability within the basolateral amygdala. In addition, we will test the
hypothesis that AEA inhibits - whereas 2-AG facilitates – the reconsolidation of labile cocaine memories and the
activation of a requisite cellular mediator of memory reconsolidation within the basolateral amygdala. To
accomplish these Aims, we will utilize sophisticated behavioral, novel optogenetic functional disconnection, and
electrophysiological recording protocols, as well as immunohistochemistry, quantitative Western blotting, and
eCB biochemical assays. Overall, renewal of this productive research program has the potential to significantly
advance our understanding of the neur...

## Key facts

- **NIH application ID:** 9896796
- **Project number:** 5R01DA025646-10
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Rita A Fuchs Lokensgard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,026
- **Award type:** 5
- **Project period:** 2010-02-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896796

## Citation

> US National Institutes of Health, RePORTER application 9896796, Context-induced Cocaine Relapse: Influence of Cocaine Memory Reconsolidation (5R01DA025646-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896796. Licensed CC0.

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