Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats

Junshi Wang, Robert W. Bina, Jeffrey C. Wingard, Ernest F. Terwilliger, Ronald P Hammer, Ella M Nikulina

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.

Original languageEnglish (US)
Pages (from-to)1009-1017
Number of pages9
JournalEuropean Journal of Neuroscience
Volume39
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Nucleus Accumbens
Amphetamine
Brain-Derived Neurotrophic Factor
Ventral Tegmental Area
tropomyosin kinase
trkB Receptor
Viruses
Dependovirus
AMPA Receptors
Mitogen-Activated Protein Kinase 3
Glutamate Receptors
Street Drugs
Locomotion
Green Fluorescent Proteins
Prefrontal Cortex
Small Interfering RNA

Keywords

  • Brain-derived neurotrophic factor
  • Cross-sensitization
  • Nucleus accumbens
  • Social stress
  • Tropomyosin-related kinase B
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats. / Wang, Junshi; Bina, Robert W.; Wingard, Jeffrey C.; Terwilliger, Ernest F.; Hammer, Ronald P; Nikulina, Ella M.

In: European Journal of Neuroscience, Vol. 39, No. 6, 2014, p. 1009-1017.

Research output: Contribution to journalArticle

@article{37cc21f6f7a143c19886a623c54ffd3f,
title = "Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats",
abstract = "The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.",
keywords = "Brain-derived neurotrophic factor, Cross-sensitization, Nucleus accumbens, Social stress, Tropomyosin-related kinase B, Ventral tegmental area",
author = "Junshi Wang and Bina, {Robert W.} and Wingard, {Jeffrey C.} and Terwilliger, {Ernest F.} and Hammer, {Ronald P} and Nikulina, {Ella M}",
year = "2014",
doi = "10.1111/ejn.12464",
language = "English (US)",
volume = "39",
pages = "1009--1017",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats

AU - Wang, Junshi

AU - Bina, Robert W.

AU - Wingard, Jeffrey C.

AU - Terwilliger, Ernest F.

AU - Hammer, Ronald P

AU - Nikulina, Ella M

PY - 2014

Y1 - 2014

N2 - The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.

AB - The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.

KW - Brain-derived neurotrophic factor

KW - Cross-sensitization

KW - Nucleus accumbens

KW - Social stress

KW - Tropomyosin-related kinase B

KW - Ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=84896118746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896118746&partnerID=8YFLogxK

U2 - 10.1111/ejn.12464

DO - 10.1111/ejn.12464

M3 - Article

C2 - 24354924

AN - SCOPUS:84896118746

VL - 39

SP - 1009

EP - 1017

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 6

ER -