A large amount of data demonstrate the importance of the locus coeruleus (LC) in the response to stress, aversive memory formation and the development of stress-related disorders; however, little is known about the effects of norepinephrine (NE) on auditory cortical activity in vitro. In the auditory cortex (ACx), NE has been reported to induce a decrease in both spontaneous and evoked signals in response to acoustic stimuli in vivo. This effect can be due to either differential modulation of basal vs. distal dendrites exerted by two classes of GABAergic interneurons (low-threshold spiking (LTS) vs. fast-spiking, (FS)), as described by recent results obtained in our laboratory, and/or by a still unknown modulation by an excitatory component. In the first part of this study, we showed that the reducing effect of bath administration of 20 μM norepinephrine (NE) on the EPSCs amplitude in different layers was judged to be postsynaptic as evidenced by an increased initial rising slope as well as an analogous reduction in the amplitude of the pressure-evoked application of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA, 500μM). NE (20μM) action on evoked EPSCs (eEPSCs) amplitude was completely blocked by 1 μM prazosin, a selective α₁-adrenoceptor antagonist, and mimicked by 1 μM phenylephrine, a selective 1-adrenoceptor agonist. Neither α2-adrenoceptor nor β-adrenoceptor blockers prevented the NE-induced decrease in synaptic efficacy. The results suggest that it is the activation of postsynaptic α1-adrenoceptors which inhibits eEPSCs throughout auditory cortex. Inhibition of EPSCs by NE was prevented by pretreatment of brain slices with PLC inhibitor, U73122, indicating that G-protein couple these receptors to their effectors. Furthermore, blockage of Ca²⁺-dependent protein kinase C with G_o-6976 did not block the effect of NE-induced eEPSC depression. The results suggested that Ca²⁺ release is not necessary for a1-mediated depression of glutamatergic synaptic transmission in auditory cortex. These findings provide evidence for a modulation role of excitatory component in auditory cortex by norepinephrine.