Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat.
Stimulation of alpha2-, especially alpha2A-adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. Alpha2-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 alpha2-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 alpha2-AR agonist clonidine and the selective alpha2A-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 alpha2-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 alpha2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism.
Ji
Xiao-Hua
XH
Institute of Neurobiology, Institutes of Brain Science, Fudan University, Shanghai, China.
Ji
Jin-Zhao
JZ
Zhang
Hui
H
Li
Bao-Ming
BM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins; D001522:Behavior, Animal; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016316:Guanfacine / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012097:Repressor Proteins; D013498:Suramin / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001426:Bacterial Proteins; C105374:NF023; D018341:Receptors, Adrenergic, alpha-2; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D015016:Yohimbine; D016316:Guanfacine; D013498:Suramin; D003000:Clonidine