title: Evaluation of Drug Concentrations Delivered by Microiontophoresis.
abstract: Microiontophoresis uses an electric current to eject a drug solution from a glass capillary and is often utilized for targeted delivery in neurochemical investigations. The amount of drug ejected, and its effective concentration at the tip, has historically been difficult to determine, which has precluded its use in quantitative studies. To address this, a method called controlled iontophoresis was developed which employs a carbon-fiber microelectrode incorporated into a multibarreled iontophoretic probe to detect the ejection of electroactive species. Here, we evaluate the accuracy of this method. To do this, we eject different concentrations of quinpirole, a D2 receptor agonist, into a brain slice containing the dorsal striatum, a brain region with a high density of dopamine terminals. Local electrical stimulation was used to evoke dopamine release, and inhibitory actions of quinpirole on this release were examined. The amount of drug ejected was estimated by detection of a coejected electrochemical marker. Dose response curves generated in this manner were compared to curves generated by conventional perfusion of quinpirole through the slice. We find several experimental conditions must be optimized for accurate results. First, selection of a marker with an identical charge was necessary to mimic the ejection of the cationic agonist. Next, evoked responses were more precise following longer periods between the end of the ejection and stimulation. Lastly, the accuracy of concentration evaluations was improved by longer ejections. Incorporation of these factors into existing protocols allows for greater certainty of concentrations delivered by controlled iontophoresis.
authors.affiliation: Department of Chemistry and ‡Neuroscience Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, 27599-3290, United States.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Kirkpatrick
authors.affiliation: Department of Chemistry and ‡Neuroscience Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, 27599-3290, United States.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wightman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D019257:Quinpirole / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole