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Distinct regulation pattern of Egr-1, BDNF and Arc during morphine-withdrawal conditioned place aversion paradigm: Role of glucocorticoids.
- Source :
-
Behavioural brain research [Behav Brain Res] 2019 Mar 15; Vol. 360, pp. 244-254. Date of Electronic Publication: 2018 Dec 11. - Publication Year :
- 2019
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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.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- AIDS-Related Complex genetics
Adrenalectomy
Animals
Avoidance Learning drug effects
Brain-Derived Neurotrophic Factor genetics
Disease Models, Animal
Early Growth Response Protein 1 genetics
Gene Expression Regulation drug effects
Glucocorticoids pharmacology
Male
Morphine adverse effects
Morphine Dependence complications
Naloxone therapeutic use
Narcotic Antagonists therapeutic use
Narcotics adverse effects
RNA, Messenger metabolism
Rats
Rats, Wistar
Substance Withdrawal Syndrome drug therapy
Substance Withdrawal Syndrome etiology
Substance Withdrawal Syndrome metabolism
AIDS-Related Complex metabolism
Brain metabolism
Brain-Derived Neurotrophic Factor metabolism
Early Growth Response Protein 1 metabolism
Glucocorticoids metabolism
Substance Withdrawal Syndrome pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7549
- Volume :
- 360
- Database :
- MEDLINE
- Journal :
- Behavioural brain research
- Publication Type :
- Academic Journal
- Accession number :
- 30550948
- Full Text :
- https://doi.org/10.1016/j.bbr.2018.12.026