Long-lasting alteration in mesocorticolimbic structures after repeated social defeat stress in rats: Time course of μ-opioid receptor mRNA and FosB/ΔFosB immunoreactivity

Ella M Nikulina, Isabel Arrillaga-Romany, Klaus A. Miczek, Ronald P Hammer

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63 Citations (Scopus)

Abstract

Social defeat stress is a salient stressor that induces neuroadaptive changes in the mesocorticolimbic dopaminergic system. Substantial evidence indicates that μ-opioid receptors (MORs) modulate dopamine transmission in the ventral tegmental area (VTA). FosB/ΔFosB protein accumulation in dopaminergic projections during repeated treatments is thought to be involved in long-term neuroplasticity. In this study we characterize the magnitude and time-course of MOR mRNA expression and FosB/ΔFosB immunoreactivity in mesocorticolimbic regions following repeated social defeat stress. Effects of brief repeated social defeat stress or control handling procedures were studied in rats either 2 h after the last exposure, or 3, 7, 14, 21 and 28 days later. We found that MOR mRNA expression in the VTA doubled after the last stress compared with handling, and remained 30-70% higher until day 21. The number of FosB/ΔFosB-labeled neurons in regions of the frontal cortex, nucleus accumbens (NAc) shell and core, and in the medial, central and basolateral amygdala increased significantly immediately after the last stress episode, and remained enhanced for 21 days. Another group of rats received bilateral intra-VTA infusion of the MOR agonist, DAMGO, 7 days after the last stress. Prior social defeat stress augmented DAMGO-induced Fos expression in the NAc shell, suggesting that Fos expression in this region might be the direct result of MOR activity in the VTA. Social defeat stress leads to an increased capacity for MOR activation in the VTA, which may be relevant to enduring FosB/ΔFosB expression in mesocorticolimbic areas and to the behaviorally sensitized response to psychostimulant drugs.

Original languageEnglish (US)
Pages (from-to)2272-2284
Number of pages13
JournalEuropean Journal of Neuroscience
Volume27
Issue number9
DOIs
StatePublished - May 2008

Fingerprint

Ventral Tegmental Area
Opioid Receptors
Messenger RNA
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Nucleus Accumbens
Neuronal Plasticity
Frontal Lobe
Dopamine
Neurons
Pharmaceutical Preparations
Proteins

Keywords

  • DAMGO
  • n. accumbens
  • Prefrontal cortex
  • Stress
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Long-lasting alteration in mesocorticolimbic structures after repeated social defeat stress in rats: Time course of μ-opioid receptor mRNA and FosB/ΔFosB immunoreactivity",
abstract = "Social defeat stress is a salient stressor that induces neuroadaptive changes in the mesocorticolimbic dopaminergic system. Substantial evidence indicates that μ-opioid receptors (MORs) modulate dopamine transmission in the ventral tegmental area (VTA). FosB/ΔFosB protein accumulation in dopaminergic projections during repeated treatments is thought to be involved in long-term neuroplasticity. In this study we characterize the magnitude and time-course of MOR mRNA expression and FosB/ΔFosB immunoreactivity in mesocorticolimbic regions following repeated social defeat stress. Effects of brief repeated social defeat stress or control handling procedures were studied in rats either 2 h after the last exposure, or 3, 7, 14, 21 and 28 days later. We found that MOR mRNA expression in the VTA doubled after the last stress compared with handling, and remained 30-70{\%} higher until day 21. The number of FosB/ΔFosB-labeled neurons in regions of the frontal cortex, nucleus accumbens (NAc) shell and core, and in the medial, central and basolateral amygdala increased significantly immediately after the last stress episode, and remained enhanced for 21 days. Another group of rats received bilateral intra-VTA infusion of the MOR agonist, DAMGO, 7 days after the last stress. Prior social defeat stress augmented DAMGO-induced Fos expression in the NAc shell, suggesting that Fos expression in this region might be the direct result of MOR activity in the VTA. Social defeat stress leads to an increased capacity for MOR activation in the VTA, which may be relevant to enduring FosB/ΔFosB expression in mesocorticolimbic areas and to the behaviorally sensitized response to psychostimulant drugs.",
keywords = "DAMGO, n. accumbens, Prefrontal cortex, Stress, Ventral tegmental area",
author = "Nikulina, {Ella M} and Isabel Arrillaga-Romany and Miczek, {Klaus A.} and Hammer, {Ronald P}",
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T2 - Time course of μ-opioid receptor mRNA and FosB/ΔFosB immunoreactivity

AU - Nikulina, Ella M

AU - Arrillaga-Romany, Isabel

AU - Miczek, Klaus A.

AU - Hammer, Ronald P

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N2 - Social defeat stress is a salient stressor that induces neuroadaptive changes in the mesocorticolimbic dopaminergic system. Substantial evidence indicates that μ-opioid receptors (MORs) modulate dopamine transmission in the ventral tegmental area (VTA). FosB/ΔFosB protein accumulation in dopaminergic projections during repeated treatments is thought to be involved in long-term neuroplasticity. In this study we characterize the magnitude and time-course of MOR mRNA expression and FosB/ΔFosB immunoreactivity in mesocorticolimbic regions following repeated social defeat stress. Effects of brief repeated social defeat stress or control handling procedures were studied in rats either 2 h after the last exposure, or 3, 7, 14, 21 and 28 days later. We found that MOR mRNA expression in the VTA doubled after the last stress compared with handling, and remained 30-70% higher until day 21. The number of FosB/ΔFosB-labeled neurons in regions of the frontal cortex, nucleus accumbens (NAc) shell and core, and in the medial, central and basolateral amygdala increased significantly immediately after the last stress episode, and remained enhanced for 21 days. Another group of rats received bilateral intra-VTA infusion of the MOR agonist, DAMGO, 7 days after the last stress. Prior social defeat stress augmented DAMGO-induced Fos expression in the NAc shell, suggesting that Fos expression in this region might be the direct result of MOR activity in the VTA. Social defeat stress leads to an increased capacity for MOR activation in the VTA, which may be relevant to enduring FosB/ΔFosB expression in mesocorticolimbic areas and to the behaviorally sensitized response to psychostimulant drugs.

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