Circadian modulation of anxiety: a role for somatostatin in the amygdala

PLoS One. 2013 Dec 20;8(12):e84668. doi: 10.1371/journal.pone.0084668. eCollection 2013.


Pharmacological evidence suggests that the neuropeptide somatostatin (SST) exerts anxiolytic action via the amygdala, but findings concerning the putative role of endogenous SST in the regulation of emotional responses are contradictory. We hypothesized that an endogenous regulation of SST expression over the course of the day may determine its function and tested both SST gene expression and the behavior of SST knock out (SST⁻/⁻) mice in different aversive tests in relation to circadian rhythm. In an open field and a light/dark avoidance test, SST⁻/⁻ mice showed significant hyperactivity and anxiety-like behavior during the second, but not during the first half of the active phase, failing to show the circadian modulation of behavior that was evident in their wild type littermates. Behavioral differences occurred independently of changes of intrinsically motivated activity in the home cage. A circadian regulation of SST mRNA and protein expression that was evident in the basolateral complex of the amygdala of wild type mice may provide a neuronal substrate for the observed behavior. However, fear memory towards auditory cue or the conditioning context displayed neither a time- nor genotype-dependent modulation. Together this indicates that SST, in a circadian manner and putatively via its regulation of expression in the amygdala, modulates behavior responding to mildly aversive conditions in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Amygdala / physiopathology*
  • Analysis of Variance
  • Animals
  • Anxiety / physiopathology*
  • Avoidance Learning / physiology
  • Circadian Rhythm / physiology*
  • Conditioning, Psychological / physiology
  • Fear / physiology
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Knockout
  • Somatostatin / genetics
  • Somatostatin / metabolism*


  • Somatostatin

Grant support

The work was supported by the German Research Foundation (SFB779 TPB5 and German Israeli Project Cooperation to OS) and by the federal state of Sachsonia-Anhalt (Center for Behavioral Brain Sciences). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.