Induction of c-Fos in 'panic/defence'-related brain circuits following brief hypercarbic gas exposure

Philip Johnson, Stephanie D. Fitz, Jacob H. Hollis, Rosario Moratalla, Stafford L. Lightman, Anantha Shekhar, Christopher A. Lowry

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Inspiration of air containing high concentrations of carbon dioxide (CO2; hypercarbic gas exposure) mobilizes respiratory, sympathetic and hypothalamic-pituitary-adrenal axis responses and increases anxiety-like behaviour in rats and humans. Meanwhile the same stimulus induces panic attacks in the majority of panic disorder patients. However, little is known about the neural circuits that regulate these acute effects. In order to determine the effects of acute hypercarbic gas exposure on forebrain and brainstem circuits, conscious adult male rats were placed in flow cages and exposed to either atmospheric air or increasing environmental CO2 concentrations (from baseline concentrations up to 20% CO2) during a 5 min period. The presence of immunoreactivity for the protein product of the immediate-early gene c-fos was used as a measure of functional cellular responses. Exposing rats to hypercarbic gas increased anxiety-related behaviour and increased numbers of c-Fos-immunoreactive cells in subcortical regions of the brain involved in: (1) the initiation of fear- or anxiety-associated behavioural responses (i.e. the dorsomedial hypothalamus, perifornical nucleus and dorsolateral and ventrolateral periaqueductal gray); (2) mobilization of the hypothalamic- pituitary-adrenal axis (i.e. the dorsomedial hypothalamus, perifornical nucleus and paraventricular hypothalamic nucleus); and (3) initiation of stress-related sympathetic responses (i.e. the dorsomedial hypothalamus, dorsolateral periaqueductal grey and rostroventrolateral medulla). These findings have implications for understanding how the brain senses changes in environmental CO2 concentrations and the neural mechanisms underlying the subsequent adaptive changes in stress-related physiology and behaviour.

Original languageEnglish
Pages (from-to)26-36
Number of pages11
JournalJournal of Psychopharmacology
Volume25
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Panic
Hypothalamus
Periaqueductal Gray
Anxiety
Gases
Panic Disorder
Brain
Air
Immediate-Early Genes
Paraventricular Hypothalamic Nucleus
Prosencephalon
Carbon Dioxide
Brain Stem
Fear
Proteins

Keywords

  • brainstem
  • circumventricular organ
  • fear
  • hypercapnia
  • hypercarbia
  • medulla
  • midbrain
  • panic
  • parabrachial nucleus
  • pons
  • solitary tract

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Psychiatry and Mental health

Cite this

Induction of c-Fos in 'panic/defence'-related brain circuits following brief hypercarbic gas exposure. / Johnson, Philip; Fitz, Stephanie D.; Hollis, Jacob H.; Moratalla, Rosario; Lightman, Stafford L.; Shekhar, Anantha; Lowry, Christopher A.

In: Journal of Psychopharmacology, Vol. 25, No. 1, 01.2011, p. 26-36.

Research output: Contribution to journalArticle

Johnson, Philip ; Fitz, Stephanie D. ; Hollis, Jacob H. ; Moratalla, Rosario ; Lightman, Stafford L. ; Shekhar, Anantha ; Lowry, Christopher A. / Induction of c-Fos in 'panic/defence'-related brain circuits following brief hypercarbic gas exposure. In: Journal of Psychopharmacology. 2011 ; Vol. 25, No. 1. pp. 26-36.
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