Exercise exerts an anxiolytic effect against repeated restraint stress through 5-HT2A-mediated suppression of the adenosine A2A receptor in the basolateral amygdala

Yea Hyun Leem, Jee Hun Jang, Jin Sun Park, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Repeated or chronic stressful stimuli induce emotion- and mood-related abnormalities, such as anxiety and depression. Conversely, regular exercise exerts protective effects. Here, we found that exercise recovered anxiety-like behaviors, as measured using the open field and elevated plus maze tests in an anxiety mouse model. In addition to behavioral improvement, exercise enhanced the synaptic density of the 5-hydroxytryptamine 2A receptor (5-HT2AR), but not the 5-HT1AR in the basolateral amygdala (BLA) region in this mouse model. Furthermore, global treatment with a selective 5-HT2AR antagonist (MDL11930) generated an anxiety phenotype. Thus, synaptic recruitment of 5-HT2AR in BLA neurons may mediate the anxiolytic effects of exercise. The exercise regimen also reduced adenosine A2A receptor (A2AR)-mediated protein kinase A (PKA) activation, and the anxiolytic effect of the exercise was blunted by local activation of A2AR within the BLA using CGS21680, a selective A2AR agonist. Particularly, A2AR-mediated PKA activity was shown to be dependent on 5-HT2AR signaling in the BLA. These results imply that repeated stress upregulates A2AR-mediated adenosine signaling to facilitate PKA activation, whereas regular exercise inhibits A2AR function by increasing 5-HT2AR in the BLA. Accordingly, this integrated modulation of 5-HT and adenosine signaling, via 5-HT2AR and A2AR respectively, may be a mechanism underlying the anxiolytic effect of regular exercise.

Original languageEnglish
Pages (from-to)182-189
Number of pages8
JournalPsychoneuroendocrinology
Volume108
DOIs
StatePublished - Oct 2019

Keywords

  • 5-HTreceptor
  • Adenosine A receptor
  • Anxiety
  • Basolateral amygdala
  • Exercise
  • Repeated stress

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