1. ¹Institute of Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China
2. ²State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China

Correspondence: Dr B-M Li, Laboratory of Higher Brain Functions, Institute of Neurobiology, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. Tel: 21 6422 1979; Fax: 21 5423 7647; E-mail: bmli@fudan.edu.cn

³These authors contributed equally to this work.

Received 8 March 2007; Revised 25 July 2007; Accepted 20 September 2007; Published online 24 October 2007.

Abstract

Stimulation of ₂-, especially _2A-adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. ₂-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 ₂-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 ₂-AR agonist clonidine and the selective _2A-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 ₂-AR antagonist yohimbine or the G_i 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 _2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.