Nicotine self-administration differentially regulates hypothalamic corticotropin-releasing factor and arginine vasopressin mRNAs and facilitates stress-induced neuronal activation

Guoliang Yu, Hao Chen, Wenyuan Zhao, Shannon G. Matta, Burt Sharp

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Abstract

Acute nicotine is a potent stimulus for activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self-administration (SA) desensitizes the ACTH response to self-administered nicotine but cross-sensitizes to mild footshock stress (mFSS). To identify underlying mechanisms, we investigated (1) the effects of chronic nicotine SA on the coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP)mRNAs,the primary hypothalamic neuropeptides regulating ACTH release, in the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS-induced activation of these neurons during nicotine SA. Adult male Sprague Dawley rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP+) neurons (twofold to threefold), reduced the number of CRF-positive (CRF+) neurons by ∼60%, but increased pcPVN CRF +/AVP+ neuronal number fivefold. Significantly, although chronic nicotine SA did not affect total c-Fos expression induced by mFSS in pcPVN CRF+ neurons, the majority of the new CRF+/AVP + population was activated by this heterotypic stressor. These phenotypic neuronal alterations may provide the pivotal mechanism underlying the capacity of chronically self-administered nicotine to cross-sensitize the HPA response to specific stressors, suggesting that nicotine may augment HPA responsiveness to specific stressors in human smokers.

Original languageEnglish (US)
Pages (from-to)2773-2782
Number of pages10
JournalJournal of Neuroscience
Volume28
Issue number11
DOIs
StatePublished - Mar 12 2008

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Pituitary Hormone-Releasing Hormones
Self Administration
Arginine Vasopressin
Corticotropin-Releasing Hormone
Nicotine
Messenger RNA
Paraventricular Hypothalamic Nucleus
Neurons
Adrenocorticotropic Hormone
Proto-Oncogene Proteins c-fos
Neuropeptides
Fluorescence In Situ Hybridization
Sprague Dawley Rats

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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title = "Nicotine self-administration differentially regulates hypothalamic corticotropin-releasing factor and arginine vasopressin mRNAs and facilitates stress-induced neuronal activation",
abstract = "Acute nicotine is a potent stimulus for activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self-administration (SA) desensitizes the ACTH response to self-administered nicotine but cross-sensitizes to mild footshock stress (mFSS). To identify underlying mechanisms, we investigated (1) the effects of chronic nicotine SA on the coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP)mRNAs,the primary hypothalamic neuropeptides regulating ACTH release, in the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS-induced activation of these neurons during nicotine SA. Adult male Sprague Dawley rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP+) neurons (twofold to threefold), reduced the number of CRF-positive (CRF+) neurons by ∼60{\%}, but increased pcPVN CRF +/AVP+ neuronal number fivefold. Significantly, although chronic nicotine SA did not affect total c-Fos expression induced by mFSS in pcPVN CRF+ neurons, the majority of the new CRF+/AVP + population was activated by this heterotypic stressor. These phenotypic neuronal alterations may provide the pivotal mechanism underlying the capacity of chronically self-administered nicotine to cross-sensitize the HPA response to specific stressors, suggesting that nicotine may augment HPA responsiveness to specific stressors in human smokers.",
author = "Guoliang Yu and Hao Chen and Wenyuan Zhao and Matta, {Shannon G.} and Burt Sharp",
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T1 - Nicotine self-administration differentially regulates hypothalamic corticotropin-releasing factor and arginine vasopressin mRNAs and facilitates stress-induced neuronal activation

AU - Yu, Guoliang

AU - Chen, Hao

AU - Zhao, Wenyuan

AU - Matta, Shannon G.

AU - Sharp, Burt

PY - 2008/3/12

Y1 - 2008/3/12

N2 - Acute nicotine is a potent stimulus for activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self-administration (SA) desensitizes the ACTH response to self-administered nicotine but cross-sensitizes to mild footshock stress (mFSS). To identify underlying mechanisms, we investigated (1) the effects of chronic nicotine SA on the coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP)mRNAs,the primary hypothalamic neuropeptides regulating ACTH release, in the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS-induced activation of these neurons during nicotine SA. Adult male Sprague Dawley rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP+) neurons (twofold to threefold), reduced the number of CRF-positive (CRF+) neurons by ∼60%, but increased pcPVN CRF +/AVP+ neuronal number fivefold. Significantly, although chronic nicotine SA did not affect total c-Fos expression induced by mFSS in pcPVN CRF+ neurons, the majority of the new CRF+/AVP + population was activated by this heterotypic stressor. These phenotypic neuronal alterations may provide the pivotal mechanism underlying the capacity of chronically self-administered nicotine to cross-sensitize the HPA response to specific stressors, suggesting that nicotine may augment HPA responsiveness to specific stressors in human smokers.

AB - Acute nicotine is a potent stimulus for activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self-administration (SA) desensitizes the ACTH response to self-administered nicotine but cross-sensitizes to mild footshock stress (mFSS). To identify underlying mechanisms, we investigated (1) the effects of chronic nicotine SA on the coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP)mRNAs,the primary hypothalamic neuropeptides regulating ACTH release, in the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS-induced activation of these neurons during nicotine SA. Adult male Sprague Dawley rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP+) neurons (twofold to threefold), reduced the number of CRF-positive (CRF+) neurons by ∼60%, but increased pcPVN CRF +/AVP+ neuronal number fivefold. Significantly, although chronic nicotine SA did not affect total c-Fos expression induced by mFSS in pcPVN CRF+ neurons, the majority of the new CRF+/AVP + population was activated by this heterotypic stressor. These phenotypic neuronal alterations may provide the pivotal mechanism underlying the capacity of chronically self-administered nicotine to cross-sensitize the HPA response to specific stressors, suggesting that nicotine may augment HPA responsiveness to specific stressors in human smokers.

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