Intensity of anxiety is modified via complex integrative stress circuitries

Justin P. Smith, Melissa A. Prince, Justin K. Achua, James M. Robertson, Raymond T. Anderson, Patrick J. Ronan, Cliff H. Summers

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress-Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of α2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic α2-adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and α2-adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalPsychoneuroendocrinology
Volume63
DOIs
StatePublished - Jan 1 2016

Fingerprint

Neuropeptides
Brain-Derived Neurotrophic Factor
Anti-Anxiety Agents
Anxiety
Aggression
Corticosterone
Learning
Phenotype
Gene Expression
CRF receptor type 1
Central Amygdaloid Nucleus
Therapeutics

Keywords

  • CRF receptors
  • Continuum
  • Exercise
  • Gradient
  • NPS
  • α receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Smith, J. P., Prince, M. A., Achua, J. K., Robertson, J. M., Anderson, R. T., Ronan, P. J., & Summers, C. H. (2016). Intensity of anxiety is modified via complex integrative stress circuitries. Psychoneuroendocrinology, 63, 351-361. https://doi.org/10.1016/j.psyneuen.2015.10.016

Intensity of anxiety is modified via complex integrative stress circuitries. / Smith, Justin P.; Prince, Melissa A.; Achua, Justin K.; Robertson, James M.; Anderson, Raymond T.; Ronan, Patrick J.; Summers, Cliff H.

In: Psychoneuroendocrinology, Vol. 63, 01.01.2016, p. 351-361.

Research output: Contribution to journalArticle

Smith, JP, Prince, MA, Achua, JK, Robertson, JM, Anderson, RT, Ronan, PJ & Summers, CH 2016, 'Intensity of anxiety is modified via complex integrative stress circuitries', Psychoneuroendocrinology, vol. 63, pp. 351-361. https://doi.org/10.1016/j.psyneuen.2015.10.016
Smith, Justin P. ; Prince, Melissa A. ; Achua, Justin K. ; Robertson, James M. ; Anderson, Raymond T. ; Ronan, Patrick J. ; Summers, Cliff H. / Intensity of anxiety is modified via complex integrative stress circuitries. In: Psychoneuroendocrinology. 2016 ; Vol. 63. pp. 351-361.
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