Endogenous Serotonin 5-HT2A and 5-HT2C Receptors Associate in the Medial Prefrontal Cortex

Amanda E. Price, Dennis J. Sholler, Sonja J. Stutz, Noelle C. Anastasio, Kathryn A. Cunningham

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The 5-HT2A receptor (5-HT2AR) and 5-HT2CR are localized to the same neurons within the medial prefrontal cortex (mPFC), which regulates executive function, decision-making, and reward-guided learning and memory processes. The 5-HT2AR and 5-HT2CR coimmunoprecipitate in the mPFC of male Sprague-Dawley rats, while in vitro studies demonstrate the presence of a physical interaction between the 5-HT2AR and 5-HT2CR. The purpose of this study was to identify mPFC subregions in which the 5-HT2AR and 5-HT2CR physically interact ex vivo in the male Sprague-Dawley rat. We established the expression patterns of 5-HT2AR and 5-HT2CR in layers I-VI of the anterior cingulate cortex (ACC), prelimbic (PL), and infralimbic (IL) subregions using double-label fluorescence immunohistochemistry in male rats. We then employed the proximity ligation assay (PLA) to test the hypothesis that the 5-HT2AR and 5-HT2CR form a close, physical association within these mPFC subregions. Our results demonstrate subregion- and layer-specific expression of the 5-HT2AR and 5-HT2CR proteins using immunofluorescence and single recognition PLA, and a spatially close (within 40 nm) interaction between the 5-HT2AR and 5-HT2CR that occurs along a dorsal-ventral gradient in the rat mPFC.

Original languageEnglish (US)
Pages (from-to)3241-3248
Number of pages8
JournalACS chemical neuroscience
Issue number7
StatePublished - Jul 17 2019


  • 5-HT receptor
  • 5-HT receptor
  • G-protein coupled receptor
  • Serotonin
  • medial prefrontal cortex
  • proximity ligation assay

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology


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