Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal

Cristina Nunez, A. Földes, M. Luisa Laorden, M. Victoria Milanes, K. Kovács

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in naïve and morphine dependent animals injected with saline or 5 mg/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2 h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Naïve rats and animals that were implanted with morphine pellets for 8 days did not display significant up-regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic-related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs.

Original languageEnglish
Pages (from-to)1060-1071
Number of pages12
JournalJournal of Neurochemistry
Volume101
Issue number4
DOIs
Publication statusPublished - May 2007

Fingerprint

Neuropeptides
Gene expression
Morphine
Naloxone
Chemical activation
Gene Expression
Neurons
Arginine Vasopressin
Corticotropin-Releasing Hormone
Rats
Corticosterone
Animals
Supraoptic Nucleus
Gene encoding
Affective Symptoms
Paraventricular Hypothalamic Nucleus
Opioid Analgesics
Hypothalamus
Up-Regulation
RNA

Keywords

  • Brainstem
  • c-Fos
  • hnRNA
  • Naloxone
  • Paraventricular nucleus
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal. / Nunez, Cristina; Földes, A.; Laorden, M. Luisa; Milanes, M. Victoria; Kovács, K.

In: Journal of Neurochemistry, Vol. 101, No. 4, 05.2007, p. 1060-1071.

Research output: Contribution to journalArticle

Nunez, Cristina ; Földes, A. ; Laorden, M. Luisa ; Milanes, M. Victoria ; Kovács, K. / Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal. In: Journal of Neurochemistry. 2007 ; Vol. 101, No. 4. pp. 1060-1071.
@article{e5441eaf2c5b45bcbf710bac75eaa565,
title = "Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal",
abstract = "Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in na{\"i}ve and morphine dependent animals injected with saline or 5 mg/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2 h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Na{\"i}ve rats and animals that were implanted with morphine pellets for 8 days did not display significant up-regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic-related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs.",
keywords = "Brainstem, c-Fos, hnRNA, Naloxone, Paraventricular nucleus, Rat",
author = "Cristina Nunez and A. F{\"o}ldes and Laorden, {M. Luisa} and Milanes, {M. Victoria} and K. Kov{\'a}cs",
year = "2007",
month = "5",
doi = "10.1111/j.1471-4159.2006.04421.x",
language = "English",
volume = "101",
pages = "1060--1071",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Activation of stress-related hypothalamic neuropeptide gene expression during morphine withdrawal

AU - Nunez, Cristina

AU - Földes, A.

AU - Laorden, M. Luisa

AU - Milanes, M. Victoria

AU - Kovács, K.

PY - 2007/5

Y1 - 2007/5

N2 - Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in naïve and morphine dependent animals injected with saline or 5 mg/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2 h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Naïve rats and animals that were implanted with morphine pellets for 8 days did not display significant up-regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic-related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs.

AB - Morphine withdrawal results in serious affective and somatic symptoms including activation of the hypothalamo-pituitary-adrenocortical (HPA) axis. To reveal secretory, activational and transcriptional changes in the hypothalamus of morphine-dependent rats during naloxone precipitated opioid withdrawal, we measured corticosterone secretion, c-Fos induction and heteronuclear (hn)RNA levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in naïve and morphine dependent animals injected with saline or 5 mg/kg naloxone. Naloxone precipitated morphine withdrawal resulted in a significant increase in corticosterone secretion and induction of neuronal activation in the hypothalamic paraventricular nucleus (PVH) 2 h after challenge. Using probes complementary to intronic sequences of genes encoding neuropeptides in parvocellular neurosecretory neurons of the PVH, we found robust increases in CRH and AVP hnRNAs in morphine dependent rats during naloxone precipitated withdrawal. Naïve rats and animals that were implanted with morphine pellets for 8 days did not display significant up-regulation of ongoing neuropeptide expression in the parvocellular compartment of the PVH. In addition to hypophyseotropic neurons, naloxone precipitated withdrawal resulted in a marked activation in autonomic-related projection neurons in PVH and in the magnocellular neurons in the PVH and supraoptic nuclei. These activations however were not associated with induction of CRH or AVP hnRNAs.

KW - Brainstem

KW - c-Fos

KW - hnRNA

KW - Naloxone

KW - Paraventricular nucleus

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=34247567169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247567169&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2006.04421.x

DO - 10.1111/j.1471-4159.2006.04421.x

M3 - Article

C2 - 17286593

AN - SCOPUS:34247567169

VL - 101

SP - 1060

EP - 1071

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -