Distinctive Roles of 5-aza-2'-deoxycytidine in Anterior Agranular Insular and Basolateral Amygdala in Reconsolidation of Aversive Memory Associated with Morphine in Rats.

Peng Liu,Nan Sui,Jianjun Zhang,Ming Li

doi:10.3389/fnbeh.2016.00050

Abstract

5-aza-2′-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases (DNMTs), has been implicated in aversive memory and the function of brain region involved in processing emotion. However, little is known about the role of 5-aza in the reconsolidation of opiate withdrawal memory. In the present study, using the morphine-naloxone induced conditioned place aversion (CPA) model in rats, we injected 5-aza into agranular insular (AI), granular insular (GI), basolateral amygdala (BLA) and central amygdala (CeA) immediately after the memory retrieval and tested the behavioral consequences at 24 h, 7 and 14 days after retrieval test. We found that 5-aza injection into AI disrupted the reconsolidation of morphine-associated withdrawal memory, but 5-aza injection into GI had no impact on the reconsolidation. Meanwhile, 5-aza injection into BLA but not CeA attenuated the withdrawal memory trace 14 days later. However, 5-aza administration to rats, in the absence of memory reactivation, had no effect on morphine-associated withdrawal memory. These findings suggest that 5-aza interferes with the reconsolidation of opiate withdrawal memory, and the roles of insular and amygdala in reconsolidation are distinctive.

Highlights

The reactivation of opiate-withdrawal memories by cues or context previously associated with withdrawal experience motivates drug-seeking behaviors and increases the risk of relapse (Luo et al, 2013)
Placements of infusion needle tips targeted at agranular insular (AI), granular insular (GI), basolateral amygdala (BLA) and central amygdala (CeA) were examined by postmortem histological verification
The results suggested that blocking DNA methyltransferases (DNMTs) in AI but not GI with 5-aza after memory reactivation disrupted the reconsolidation of established conditioned place aversion (CPA)

Summary

Introduction

The reactivation of opiate-withdrawal memories by cues or context previously associated with withdrawal experience motivates drug-seeking behaviors and increases the risk of relapse (Luo et al, 2013). Insular cortex and amygdala are the key brain regions for manipulating the drug-related memory reconsolidation (Hellemans et al, 2006; Contreras et al, 2012). Studies implicate an indispensable role for the basolateral amygdala (BLA) in the reconsolidation of drug-related withdrawal memories (Hellemans et al, 2006). With regard to the central amygdala (CeA), which is implicated in drug withdrawal-induced conditioned place aversion (CPA; Watanabe et al, 2003), appears to be selectively involved in mediating the reconsolidation of alcohol-related memories (Barak et al, 2013). There are massive reciprocal connections between the insular cortex and the amygdala (Moraga-Amaro and Stehberg, 2012). The amygdala projection from the insular cortex appears to be organized and targeted all levels of the intra-amygdala connections linking the lateral, basolateral and central nuclei, turning to motivate behaviors (Shi and Cassell, 1998)

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Results

Conclusion