Monitoring Dopamine Responses to Potassium Ion and Nomifensine by in Vivo Microdialysis with Online Liquid Chromatography at One-Minute Resolution

Abstract

Recently, our laboratory has demonstrated the technical feasibility of monitoring dopamine at one-min temporal resolution with microdialysis and online liquid chromatography. Here, we monitor dopamine in the rat striatum during local delivery of high potassium/low sodium or nomifensine in awake-behaving rats. Microdialysis probes were implanted and perfused continuously with or without dexamethasone in the perfusion fluid for four days. Dexamethasone is an anti-inflammatory agent that exhibits several positive effects on the apparent health of the brain tissue surrounding microdialysis probes. Dopamine was monitored one or four days after implantation under basal conditions, during 10-min applications of 60 mM or 100 mM K+, and during 15-min applications of 10 μM nomifensine. High K + or nomifensine were delivered locally by adding them to the microdialysis perfusion fluid using a computer-controlled, low-dead-volume six-port valve. Each day/K+/dexamethasone combination elicited specific dopamine responses. Dexamethasone treatment increased dopamine levels in basal dialysates (i.e., in the absence of K+ or nomifensine). Applications of 60 mM K+ evoked distinct responses on days one and four after probe implantation, depending upon the presence or absence of dexamethasone, consistent with dexamethasone’s ability to mitigate the traumatic effect of probe implantation. Applications of 100 mM K+ evoked dramatic oscillations in dopamine levels that correlated with changes in the field potential at a metal electrode implanted adjacent to the microdialysis probe. This combination of results indicates the role of spreading depolarization in response to 100 mM K+. With one-min temporal resolution we find that it is possible to characterize the pharmacokinetics of the response to the local delivery of nomifensine. Overall, the findings reported here confirm the benefits arising from the ability to monitor dopamine via microdialysis at high sensitivity and at high temporal resolution.

Development of Glass‐sealed Gold Nanoelectrodes for in vivo Detection of Dopamine in Rat Brain

“…When 20 mg kg −1 nomifensine (a dopamine reuptake blocker) was exogenously infused into abdomen, the amperometric response increased immediately, indicating an increase in the extracellular level of DA in response to nomifensine treatment. According to the calibration curve(Figure B), the concentration of DA release evoked by nomifensine was estimated to be 37 nM, which was relatively close to the reported values (Table S1) . This is the first time that concentration of DA in rat brain after nomifensine injection is reported by glass‐sealed Au nanoelectrode.…”

An implantable multimodal sensor for oxygen, neurotransmitters, and electrophysiology during spreading depolarization in the deep brain

“…Other studies with combined electrophysiology and dopamine recordings have been unable to discern the difference in onset time for the two signals. 12, 29, 30 With our time-locked recordings at high temporal resolution (5 Hz), we found that the DA signal onset followed the DC potential onset by 6.8 ± 0.9 s (average ± SEM, n = 8 subjects).…”

“…44 We obtained peak values of 8.2 ± 1.7 μM dopamine (n = 7 subjects), which agrees with recordings made during SD in the striatum with less selective voltammetric techniques and, more recently, with microdialysis. 12, 29, 30 It is important to keep in mind that calibration curves for dopamine with FSCV deviate from linearity above ~5 μM, 44 which could lead to an underestimation of the concentration. Also, during SD, the extracellular space shrinks, causing an enhanced increase in concentration for a given increase in quantity of a species.…”

DNA-stabilized silver nanoclusters as specific, ratiometric fluorescent dopamine sensors

“…Basal dopamine concentrations in relevant brain areas, including the extracellular matrix of the striatum, are commonly 1nM-1µM, though they can be higher in the vicinity of the synapse shortly after release. 7,[35][36][37][38] While the synthesis-dependent signal from DNA S4-AgNCs is sensitive in this range (10 nM -100 µM), the sensitivity and working range of the post-synthesis responsive (and therefore in vivo compatible) DNA S5-AgNC nanosensor (1-100 µM) falls outside these commonly measured values. Ratiometric fluorescent sensors are generally challenging to engineer, 34 but the sequence modularity of DNA-AgNCs offers a flexible new toolkit.…”