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 α2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.
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Acknowledgements
This work was supported by grants to Bao-Ming Li from the Ministry of Science and Technology of China (2006CB500807), the Ministry of Education of China (Program for Changjiang Scholars and Innovative Research Team in University), and the National Natural Science Foundation of China (30225023, 30430240, 30611120530). Technical assistance of Xu Kai-Jing is gratefully acknowledged.
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The authors declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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Ji, XH., Ji, JZ., Zhang, H. et al. Stimulation of α2-Adrenoceptors Suppresses Excitatory Synaptic Transmission in the Medial Prefrontal Cortex of Rat. Neuropsychopharmacol 33, 2263–2271 (2008). https://doi.org/10.1038/sj.npp.1301603
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DOI: https://doi.org/10.1038/sj.npp.1301603
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