Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment

Yafang Zhang, Elizabeth J. Crofton, Dingge Li, Mary Kay Lobo, Xiuzhen Fan, Eric J. Nestler, Thomas Green

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.

Original languageEnglish (US)
Article number297
JournalFrontiers in Behavioral Neuroscience
Volume8
Issue numberAUG
DOIs
StatePublished - Aug 29 2014

Fingerprint

Nucleus Accumbens
Cocaine
Depression
Phenotype
Self Administration
Hunger
Street Drugs
Reward
Psychological Stress
Sucrose
Transcription Factors
Anxiety
Brain
Proteins

Keywords

  • Adeno-associated virus (AAV)
  • Cocaine self administration
  • Depression
  • Environmental enrichment
  • Overexpression
  • ΔFosB

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology

Cite this

Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment. / Zhang, Yafang; Crofton, Elizabeth J.; Li, Dingge; Lobo, Mary Kay; Fan, Xiuzhen; Nestler, Eric J.; Green, Thomas.

In: Frontiers in Behavioral Neuroscience, Vol. 8, No. AUG, 297, 29.08.2014.

Research output: Contribution to journalArticle

@article{d4405b0d40cd458d8e322029d8a1c277,
title = "Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment",
abstract = "Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.",
keywords = "Adeno-associated virus (AAV), Cocaine self administration, Depression, Environmental enrichment, Overexpression, ΔFosB",
author = "Yafang Zhang and Crofton, {Elizabeth J.} and Dingge Li and Lobo, {Mary Kay} and Xiuzhen Fan and Nestler, {Eric J.} and Thomas Green",
year = "2014",
month = "8",
day = "29",
doi = "10.3389/fnbeh.2014.00297",
language = "English (US)",
volume = "8",
journal = "Frontiers in Behavioral Neuroscience",
issn = "1662-5153",
publisher = "Frontiers Research Foundation",
number = "AUG",

}

TY - JOUR

T1 - Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment

AU - Zhang, Yafang

AU - Crofton, Elizabeth J.

AU - Li, Dingge

AU - Lobo, Mary Kay

AU - Fan, Xiuzhen

AU - Nestler, Eric J.

AU - Green, Thomas

PY - 2014/8/29

Y1 - 2014/8/29

N2 - Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.

AB - Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.

KW - Adeno-associated virus (AAV)

KW - Cocaine self administration

KW - Depression

KW - Environmental enrichment

KW - Overexpression

KW - ΔFosB

UR - http://www.scopus.com/inward/record.url?scp=84982764466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84982764466&partnerID=8YFLogxK

U2 - 10.3389/fnbeh.2014.00297

DO - 10.3389/fnbeh.2014.00297

M3 - Article

VL - 8

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

IS - AUG

M1 - 297

ER -