Distinct regulation pattern of Egr-1, BDNF and Arc during morphine-withdrawal conditioned place aversion paradigm

Role of glucocorticoids

Daniel García-Pérez, Szilamer Ferenczi, K. Kovács, M. Victoria Milanés

Research output: Contribution to journalArticle

Abstract

Negative affective aspects of opiate abstinence contribute to the persistence of substance abuse. Importantly, interconnected brain areas involved in aversive motivational processes, such as the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), become activated when animals are confined to withdrawal-paired environments. In the present study, place aversion was elicited in sham and adrenalectomized (ADX) animals by conditioned naloxone-precipitated drug withdrawal following exposure to chronic morphine. qPCR was employed to detect the expression of brain derived neurotrophic factor (Bdnf) and the immediate early genes (IEG) early growth response 1 (Egr-1) and activity-regulated cytoskeletal-associated protein (Arc) mRNAs in the VTA and mPFC at different time points of the conditioned place aversion (CPA) paradigm: after the conditioning phase and after the test phase. Sham + morphine rats exhibited robust CPA, which was impaired in ADX + morphine animals. Egr-1 and Arc were induced in the VTA and mPFC after morphine-withdrawal conditioning phase. Furthermore, Bdnf expression was enhanced in the VTA during the test phase. Bdnf induction seemed to be glucocorticoid-dependent, given that was correlated with HPA axis function and was not observed in morphine-dependent ADX animals. In addition, BDNF regulation and function was opposite in the VTA and mPFC during aversive-withdrawal memory retrieval. Our results suggest that IEGs and BDNF in these brain regions may play key roles in mediating the negative motivational component of opiate withdrawal.

Original languageEnglish
Pages (from-to)244-254
Number of pages11
JournalBehavioural Brain Research
Volume360
DOIs
Publication statusPublished - Mar 15 2019

Fingerprint

Ventral Tegmental Area
Brain-Derived Neurotrophic Factor
Morphine
Glucocorticoids
Prefrontal Cortex
Opiate Alkaloids
Growth
Immediate-Early Genes
Brain
Naloxone
Substance-Related Disorders
activity regulated cytoskeletal-associated protein
Messenger RNA
Pharmaceutical Preparations

Keywords

  • Adrenalectomy
  • Medial prefrontal cortex
  • Morphine withdrawal aversive memories
  • Ventral tegmental area

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Distinct regulation pattern of Egr-1, BDNF and Arc during morphine-withdrawal conditioned place aversion paradigm : Role of glucocorticoids. / García-Pérez, Daniel; Ferenczi, Szilamer; Kovács, K.; Milanés, M. Victoria.

In: Behavioural Brain Research, Vol. 360, 15.03.2019, p. 244-254.

Research output: Contribution to journalArticle

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