In vivo comparison of norepinephrine and dopamine release in rat brain by simultaneous measurements with fast‐scan cyclic voltammetry

Abstract

Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. Here, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the two catecholamines was measured simultaneously using fast-scan cyclic voltammetry (FSCV) at two different carbon-fiber microelectrodes, each implanted in the brain region of interest. Simultaneous dopamine and norepinephrine release was evoked by electrical stimulation of a region where the ventral noradrenergic bundle (VNB), the pathway of noradrenergic neurons, courses through the ventral tegmental area/substantia nigra (VTA/SN), the origin of dopaminergic cell bodies. The release and uptake of norepinephrine in the vBNST were both significantly slower than for dopamine in the NAc. Pharmacological manipulations in the same animal demonstrated that the two catecholamines are differently regulated. The combination of a dopamine autoreceptor antagonist and amphetamine significantly increased basal extracellular dopamine whereas a norepinephrine autoreceptor antagonist and amphetamine did not change basal norepinephrine concentration. α-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, decreased electrically evoked dopamine release faster than norepinephrine. The dual-microelectrode FSCV technique along with anatomical and pharmacological evidence confirms that dopamine in the NAc and norepinephrine in the vBNST can be monitored selectively and simultaneously in the same animal. The high temporal and spatial resolution of the technique enabled us to examine differences in the dynamics of extracellular norepinephrine and dopamine concurrently in two different limbic structures.

Brain dopamine and serotonin differ in regulation and its consequences

“…In prior work we used a similar comparative approach to compare release of norepinephrine and dopamine evoked by a single stimulation and found that their release and uptake characteristics were quite similar (29). In this work, high time resolution recordings revealed much greater differences in regulation of dopamine and 5-HT.…”

“…5E) that persists throughout the remainder of the experiment (P < 0.05). Stimulation at a common site that releases different neurotransmitters provides a way to compare dynamic alterations in their regulatory mechanisms (29). A particularly noteworthy finding was that dopamine release was ∼300 times greater than 5-HT release, despite similar tissue content in the two regions examined [90 ng/mg protein for dopamine in the NAc (16) and 21 ng mg −1 protein for 5-HT in the SNr (30)].…”

Cross-hemispheric dopamine projections have functional significance

“…To investigate connectivity between hemispheres, we measured dopamine transients bilaterally in the NAc of freely moving rats. We recorded from dual carbon fiber electrodes, as used previously in anesthetized animals (36). We targeted guide cannulas over the NAc (Fig.…”

Nonequilibrium Activation of a G-Protein-Coupled Receptor

“…Once released, it diffuses across the synaptic space and exerts its function by binding to and activating either presynaptic ␣ 2A -ARs on the nerve ending or postsynaptic ␣ 2A -ARs on the effector organ. Fast cyclic voltammetry measurements in multiple brain regions have shown that the maximal evoked norepinephrine release in vivo is in the micromolar range and that the time required for the overflow to decay to half of the maximum is a few seconds (Park et al, 2009(Park et al, , 2011.…”