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

摘要

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.