Norepinephrine (NE) is also an important catecholamine modulator of PFC function and NE neurons that innervate the PFC originate in the locus ceruleus. NE content is generally lower in the PFC than dopamine and NE fibers appear to target more superficial layers as compared to dopamine. NE’s effects on PFC neuronal function are mediated primarily by α1, α2a, and β1 adrenergic receptors. Its affinity for these subtypes is greatest for α2a receptors and this subtype is thought to underlie most of NE’s modulation of PFC function during normal, nonstressed waking conditions. The effects of methylphenidate, an indirect NE agonist, on the intrinsic excitability of deep-layer PFC pyramidal neurons have recently been studied using whole-cell patch clamp electrophysiology (Andrews and Lavin, 2006). Methylphenidate enhanced current-evoked spike activity and this effect was blocked by α2a antagonists but not those selective for α1 or β1 receptors. Interestingly, the effect of methylphenidate on firing rate was abolished when blockers of synaptic transmission were added to the bath suggesting that NE may suppress the activity of fast-spiking interneurons that normally regulate pyramidal neuron excitability. In
