Stimulation of α2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat

Xiao Hua Ji, Jin Zhao Ji, Hui Zhang, Bao Ming Li*

*Corresponding author for this work

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Stimulation of α2-, especially α2A- adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. α2-Adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for treatment of psychiatric disorders such as attention-deficit/ hyperactivity disorder (ADHD) and schizophrenia. However, the neurophysiological actions of α2-ARs in the PFC are poorly understood. In the present study, we recorded field excitatory post-synaptic potential (fEPSP) and evoked excitatory post-synaptic current (eEPSC) in the medial prefrontal cortex (mPFC) of rats, using in vivo field-potential recording and in vitro whole-cell patch-clamp recording techniques, and examined the effects of the α2-AR agonist clonidine and the selective α2A- AR agonist guanfacine on fEPSP and eEPSC. Systemic or intra-mPFC application of clonidine or guanfacine significantly reduced fEPSP in the mPFC, either in anesthetized or freely moving rats. Consistently, bath-application of guanfacine suppressed eEPSC in layer V/VI pyramidal neurons, and this effect was blocked by the α2-AR antagonist yohimbine or the Gi inhibitor NF023. Moreover, treatment with guanfacine had no effect on paired-pulse facilitation (PPF) of fEPSP and eEPSC. The present study provides the first electrophysiological evidence that stimulation of α 2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.

Original languageEnglish (US)
Pages (from-to)2263-2271
Number of pages9
JournalNeuropsychopharmacology
Volume33
Issue number9
DOIs
StatePublished - Aug 1 2008

Keywords

  • α-adrenoceptor
  • EPSC
  • fEPSP
  • Medial prefrontal cortex
  • Rat

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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