Mapping functional traces of opioid memories in the rat brain - Inria - Institut national de recherche en sciences et technologies du numérique
Preprints, Working Papers, ... Year : 2023

Mapping functional traces of opioid memories in the rat brain

Abstract

Addiction to psychoactive substances is a maladaptive learned behavior. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse triggering ability. Here we asked where context and salience might be concurrently represented in the brain, and found circuitry hubs specific to morphine-related contextual information storage. Starting with a classical rodent morphine-conditioned place preference (CPP) apparatus, we developed a CPP protocol that allows stimuli presentation inside a magnetic resonance imaging scanner, to allow the investigation of whole brain activity during retrieval of drug-context paired associations, as well as resting state functional connectivity under the effect of morphine conditioning. Using fMRI we found context-specific responses to stimulus onset in multiple brain regions, namely limbic, sensory, and striatal. Furthermore, we found increased functional connectivity of lateral septum with regions within and beyond a proposed limbic network, and of the lateral habenula with hippocampal CA1 region, in response to repeated pairings of drug and context. Subsequent exposure to either morphine or saline-conditioned contexts led to significant, context-specific, functional interconnectivity among amygdala, lateral habenula, and lateral septum. Resting-state connectivity of the lateral habenula and amygdala, and that during saline-paired context presentation significantly predicted inter-individual CPP score differences. In sum, our findings show that drug- and saline-paired contexts form distinct memory traces in overlapping functional brain microcircuits, and intrinsic connectivity of habenula, septum, and amygdala likely influences the maladaptive contextual learning in response to opioids. We identify functional mechanisms involved in the acquisition and retrieval of drug-related memories that might be behind the relapse-triggering ability of opioid-associated sensory/contextual cues.
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hal-04389077 , version 1 (11-01-2024)

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Joana Gomes-Ribeiro, João Martins, José Sereno, Samuel Deslauriers-Gauthier, Teresa Summavielle, et al.. Mapping functional traces of opioid memories in the rat brain. 2024. ⟨hal-04389077⟩
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