Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor

Seema Bhatnagar, Linda M. Sun, Jacob Raber, Stephen Maren, David Julius, Mary F. Dallman

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The serotonin-3 (5-HT-3A) receptor has been localized in limbic and brainstem structures that regulate anxiety-related behavior and hypothalamic-pituitary-adrenal (HPA) activity, but its role in regulating anxiety-related behaviors is equivocal, and evidence for its role in regulating HPA activity is limited. Therefore, we used 5-HT-3A receptor knockout (KO) mice to further study these issues. Behavior in the elevated plus maze, open field, light-dark box and after Pavlovian fear conditioning was examined in addition to HPA activity under basal and acute stress conditions. Compared to age-matched adult male wild-type (WT) controls, adult male KO mice exhibited increased distance traveled in the open arms of the elevated plus maze, consistent with decreased measures of anxiety. There were no differences between the two genotypes in exploratory behavior in the open field or light-dark test. KO mice displayed enhanced fear conditioning indexed by fear-induced freezing behavior. KO mice displayed lower adrenocorticotropin (ACTH) responses to restraint or lipopolysaccharide (LPS). In addition, lower vasopressin mRNA in the paraventricular nucleus of the hypothalamus (PVN) and higher corticotropin-releasing hormone (CRH) mRNA in the central amygdala were observed in KO compared to WT mice. Therefore, deletion of the 5-HT-3A receptor revealed an important role for this receptor in regulating HPA responses to acute stress and a potential interaction between the 5-HT-3A receptor and CRH in the amygdala. Together, these data suggest that the 5-HT-3A receptor does not have a unitary role in the regulation of anxiety- and fear-related behaviors but has a potentially substantial role in the regulation of HPA activity.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalPhysiology and Behavior
Volume81
Issue number4
DOIs
StatePublished - Jun 2004

Fingerprint

Serotonin Receptors
Anxiety
Knockout Mice
Fear
Corticotropin-Releasing Hormone
Adrenocorticotropic Hormone
Light
Messenger RNA
Exploratory Behavior
Paraventricular Hypothalamic Nucleus
Amygdala
Vasopressins
Freezing
Hypothalamus
Brain Stem
Lipopolysaccharides
Serotonin
Genotype
Conditioning (Psychology)

Keywords

  • Amygdala
  • Anxiety
  • CRH
  • Serotonin-3 receptor
  • Stress
  • Vasopressin

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Physiology (medical)

Cite this

Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor. / Bhatnagar, Seema; Sun, Linda M.; Raber, Jacob; Maren, Stephen; Julius, David; Dallman, Mary F.

In: Physiology and Behavior, Vol. 81, No. 4, 06.2004, p. 545-555.

Research output: Contribution to journalArticle

Bhatnagar, Seema ; Sun, Linda M. ; Raber, Jacob ; Maren, Stephen ; Julius, David ; Dallman, Mary F. / Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor. In: Physiology and Behavior. 2004 ; Vol. 81, No. 4. pp. 545-555.
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