Acute serotonergic treatment changes the relation between anxiety and HPA-axis functioning and periaqueductal gray activation

D. Hestermann, Y. Temel, A. Blokland, L.W. Lim

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Serotonergic (5-HT) drugs are widely used in the clinical management of mood and anxiety disorders. However, it is reported that acute 5-HT treatment elicits anxiogenic-like behaviour. Alterations of the 5-HT system and the hypothalamic-pituitary-adrenal (HPA) axis have for a long time been implicated in anxiety. Interestingly, the periaqueductal gray (PAG), a midbrain structure which regulates anxiety behaviour - has robust 5-HT fibers and reciprocal connections with the paraventricular nucleus of the hypothalamus of the HPA axis. Although the HPA axis and the 5-HT system are well investigated, the relationship between the stress hormones induced by 5-HT drug treatment and the PAG neural correlates of the behaviour remain largely unknown. In this study, the effects of acute and chronic treatments with buspirone (BUSP) and escitalopram (ESCIT) on anxiety-related behaviours were tested in an open-field (OF). The treatment effects on c-Fos immunoreactivity (c-Fos-ir) in different regions of the PAG were investigated. The corticosterone (CORT) concentration was measured in order to determine the neural-endocrine correlates of anxiety-related behaviours and drug treatments. Our results demonstrate that acute BUSP and ESCIT treatments induced anxiogenic behaviours with elevation of CORT when compared to the baseline. A decrease of c-Fos-ir was found only in the dorsomedial PAG region of both the treatment groups. Correlation analysis showed that the CORT were not associated with the OF anxiogenic behaviour and PAG c-Fos-ir. No significant differences were found in terms of behaviours and CORT after chronic treatment. In conclusion, acute BUSP and ESCIT treatments elicited anxiogenic response with activation of the HPA axis and reduction of c-Fos-ir in the dorsomedial PAG. Although no correlation was found between the stress hormone and the PAG c-Fos-ir, this does not imply the lack of cause-and-effect relationship between neuroendocrine effects and PAG function in anxiety responses. These correlation studies suggest that the regulation of 5-HT system was probably disrupted by acute 5-HT treatment.
Original languageEnglish
Pages (from-to)155-165
Number of pages11
JournalBehavioural Brain Research
Volume273
Early online date18 Jul 2014
DOIs
Publication statusPublished - 14 Oct 2014

Keywords

  • ANXIOLYTIC EFFICACY
  • Anxiety
  • CHRONIC FLUOXETINE
  • CITALOPRAM TREATMENT
  • CORTICOTROPIN-RELEASING-FACTOR
  • FOS EXPRESSION
  • GREY-MATTER
  • HYPOTHALAMIC PARAVENTRICULAR NUCLEUS
  • Hypothalamic-pituitary-adrenal axis
  • PANIC DISORDER
  • PITUITARY-ADRENAL AXIS
  • Periaqueductal gray
  • RESTRAINT STRESS
  • Serotonin
  • Stress hormone

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