Modulatory effects of norepinephrine, acting on alpha1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress

Marco Cecchi, Habibeh Khoshbouei, David A Morilak

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

The central nucleus of the amygdala (CeA) is a component of the limbic fear-anxiety circuit, and has also been implicated in regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic innervation, and is rich in expression of α1-adrenergic receptors. We hypothesized that norepinephrine (NE), acting on α1 receptors in CeA, may modulate stress-induced anxiety-like behavioral responses and HPA activation. To investigate the role of α1 adrenergic receptors in CeA on stress-induced behavioral reactivity, the α1 antagonist benoxathian was microinjected bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral responses to acute immobilization stress were measured on the Social Interaction (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently blocked the reduction in SI time induced by immobilization stress, whereas β-receptor antagonists had no effect, consistent with an absence of β-receptors in CeA. By contrast, in separate experiments, benoxathian had no effect on stress-induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress-induced plasma ACTH secretion. These results confirm that the SI test and EPMZ measure different aspects of behavioral stress reactivity that can be modulated independently, and likewise, that noradrenergic modulation of behavioral stress reactivity can occur independently of modulation of the HPA axis.

Original languageEnglish (US)
Pages (from-to)1139-1147
Number of pages9
JournalNeuropharmacology
Volume43
Issue number7
DOIs
StatePublished - Dec 2002

Fingerprint

Immobilization
Norepinephrine
Interpersonal Relations
Anxiety
Adrenergic Receptors
Exploratory Behavior
Adrenocorticotropic Hormone
Fear
Sprague Dawley Rats
Central Amygdaloid Nucleus
benoxathian

Keywords

  • ACTH
  • Anxiety-like behavior
  • Benoxathian
  • Elevated plus-maze
  • HPA axis
  • Social interaction

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

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title = "Modulatory effects of norepinephrine, acting on alpha1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress",
abstract = "The central nucleus of the amygdala (CeA) is a component of the limbic fear-anxiety circuit, and has also been implicated in regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic innervation, and is rich in expression of α1-adrenergic receptors. We hypothesized that norepinephrine (NE), acting on α1 receptors in CeA, may modulate stress-induced anxiety-like behavioral responses and HPA activation. To investigate the role of α1 adrenergic receptors in CeA on stress-induced behavioral reactivity, the α1 antagonist benoxathian was microinjected bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral responses to acute immobilization stress were measured on the Social Interaction (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently blocked the reduction in SI time induced by immobilization stress, whereas β-receptor antagonists had no effect, consistent with an absence of β-receptors in CeA. By contrast, in separate experiments, benoxathian had no effect on stress-induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress-induced plasma ACTH secretion. These results confirm that the SI test and EPMZ measure different aspects of behavioral stress reactivity that can be modulated independently, and likewise, that noradrenergic modulation of behavioral stress reactivity can occur independently of modulation of the HPA axis.",
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N2 - The central nucleus of the amygdala (CeA) is a component of the limbic fear-anxiety circuit, and has also been implicated in regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic innervation, and is rich in expression of α1-adrenergic receptors. We hypothesized that norepinephrine (NE), acting on α1 receptors in CeA, may modulate stress-induced anxiety-like behavioral responses and HPA activation. To investigate the role of α1 adrenergic receptors in CeA on stress-induced behavioral reactivity, the α1 antagonist benoxathian was microinjected bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral responses to acute immobilization stress were measured on the Social Interaction (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently blocked the reduction in SI time induced by immobilization stress, whereas β-receptor antagonists had no effect, consistent with an absence of β-receptors in CeA. By contrast, in separate experiments, benoxathian had no effect on stress-induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress-induced plasma ACTH secretion. These results confirm that the SI test and EPMZ measure different aspects of behavioral stress reactivity that can be modulated independently, and likewise, that noradrenergic modulation of behavioral stress reactivity can occur independently of modulation of the HPA axis.

AB - The central nucleus of the amygdala (CeA) is a component of the limbic fear-anxiety circuit, and has also been implicated in regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic innervation, and is rich in expression of α1-adrenergic receptors. We hypothesized that norepinephrine (NE), acting on α1 receptors in CeA, may modulate stress-induced anxiety-like behavioral responses and HPA activation. To investigate the role of α1 adrenergic receptors in CeA on stress-induced behavioral reactivity, the α1 antagonist benoxathian was microinjected bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral responses to acute immobilization stress were measured on the Social Interaction (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently blocked the reduction in SI time induced by immobilization stress, whereas β-receptor antagonists had no effect, consistent with an absence of β-receptors in CeA. By contrast, in separate experiments, benoxathian had no effect on stress-induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress-induced plasma ACTH secretion. These results confirm that the SI test and EPMZ measure different aspects of behavioral stress reactivity that can be modulated independently, and likewise, that noradrenergic modulation of behavioral stress reactivity can occur independently of modulation of the HPA axis.

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