In vivo voltammetry monitoring of electrically evoked extracellular norepinephrine in subregions of the bed nucleus of the stria terminalis

Abstract

Norepinephrine (NE) is an easily oxidized neurotransmitter that is found throughout the brain. Considerable evidence suggests that it plays an important role in neurocircuitry related to fear and anxiety responses. In certain subregions of the bed nucleus of the stria terminalis (BNST), NE is found in large amounts. In this work we probed differences in electrically evoked release of NE and its regulation by the norepinephrine transporter (NET) and the α(2)-adrenergic autoreceptor (α(2)-AR) in two regions of the BNST of anesthetized rats. NE was monitored in the dorsomedial BNST (dmBNST) and ventral BNST (vBNST) by fast-scan cyclic voltammetry at carbon fiber microelectrodes. Pharmacological agents were introduced either by systemic application (intraperitoneal injection) or by local application (iontophoresis). The iontophoresis barrels were attached to a carbon fiber microelectrode to allow simultaneous detection of evoked NE release and quantitation of iontophoretic delivery. Desipramine (DMI), an inhibitor of NET, increased evoked release and slowed clearance of released NE in both regions independent of the mode of delivery. However, the effects of DMI were more robust in the vBNST than in the dmBNST. Similarly, the α(2)-AR autoreceptor inhibitor idazoxan (IDA) enhanced NE release in both regions but to a greater extent in the vBNST by both modes of delivery. Since both local application by iontophoresis and systemic application of IDA had similar effects on NE release, our results indicate that terminal autoreceptors play a predominant role in the inhibition of subsequent release.