title: Localized drug application and sub-second voltammetric dopamine release measurements in a brain slice perfusion device.
abstract: The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last 2 decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of the neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices. The device incorporates a microfluidic channel that runs under the perfusion bath and a microcapillary that supplies fluid from this channel up to the slice. We measured electrically evoked DA release in brain slices before and after the administration of two dopaminergic stimulants, cocaine and GBR-12909. Measurements were collected at two locations, one directly over and the other 500 μm away from the capillary opening. Using this approach, the controlled delivery of drugs to a confined region of the brain slice and the application of this chamber to FSCV measurements, were demonstrated. Moreover, the consumption of drugs was reduced to tens of microliters, which is thousands of times less than traditional perfusion methods. We expect that this simply fabricated device will be useful in providing spatially resolved delivery of drugs with minimum consumption for voltammetric and electrophysiological studies of a variety of biological tissues both in vitro and ex vivo.
authors.affiliation: Department of Chemistry and R. N. Adams Institute for Bioanalytical Chemistry, University of Kansas , Lawrence, Kansas 66045 United States.
authors.forename: Meng
authors.initials: M
authors.lastname: Sun
authors.forename: Sam V
authors.initials: SV
authors.lastname: Kaplan
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Gehringer
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Limbocker
authors.forename: Michael A
authors.initials: MA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D016503:Drug Delivery Systems; D066298:In Vitro Techniques
chemical_list: D004298:Dopamine
references.citation: J Neurosci Methods. 2013 Oct 15;219(2):292-6
references.pmid: 23969260
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11510-5
references.pmid: 22778401
references.citation: Lab Chip. 2011 Jul 7;11(13):2247-54
references.pmid: 21562669
references.citation: Nature. 2003 Apr 10;422(6932):614-8
references.pmid: 12687000
references.citation: Neuron. 2005 Apr 7;46(1):65-74
references.pmid: 15820694
references.citation: ACS Chem Neurosci. 2010 Jul 1;1(9):627-638
references.pmid: 21060714
references.citation: Biomed Microdevices. 2010 Oct;12(5):761-7
references.pmid: 20464499
references.citation: J Neurophysiol. 2001 Jun;85(6):2468-76
references.pmid: 11387393
references.citation: Lab Chip. 2007 Jul;7(7):842-9
references.pmid: 17594002
references.citation: Crit Rev Ther Drug Carrier Syst. 1994;11(2-3):161-213
references.pmid: 7600587
references.citation: Lab Chip. 2010 Feb 7;10(3):326-34
references.pmid: 20091004
references.citation: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7781-6
references.pmid: 15136721
references.citation: Anal Chem. 2011 Jul 1;83(13):5207-13
references.pmid: 21604670
references.citation: Clin Chem. 2003 Oct;49(10):1763-73
references.pmid: 14500617
references.citation: ACS Chem Neurosci. 2013 May 15;4(5):782-9
references.pmid: 23556461
references.citation: Lab Chip. 2013 Feb 21;13(4):509-21
references.pmid: 23306275
references.citation: Lab Chip. 2013 May 7;13(9):1666-76
references.pmid: 23474943
references.citation: Anal Chem. 2008 Nov 15;80(22):8635-41
references.pmid: 18947198
references.citation: PLoS One. 2013 May 03;8(5):e60763
references.pmid: 23671560
references.citation: J Neurochem. 2010 Feb;112(3):755-61
references.pmid: 19929911
references.citation: J Neurosci. 2011 Jul 27;31(30):10829-35
references.pmid: 21795535
references.citation: Nature. 1996 Feb 15;379(6566):606-12
references.pmid: 8628395
references.citation: J Neurosci. 2006 Mar 22;26(12):3206-9
references.pmid: 16554471
references.citation: Neuron. 2007 Apr 19;54(2):237-44
references.pmid: 17442245
references.citation: Lab Chip. 2013 Feb 21;13(4):527-35
references.pmid: 23042571
references.citation: Lab Chip. 2012 Jun 21;12(12):2103-17
references.pmid: 22534786
references.citation: Anal Chem. 2002 Jun 15;74(12):2623-36
references.pmid: 12090653
references.citation: J Neurochem. 2006 May;97(3):737-46
references.pmid: 16573654
references.citation: Anal Chem. 2004 Oct 1;76(19):5697-704
references.pmid: 15456288
references.citation: Nature. 2006 Jul 27;442(7101):368-73
references.pmid: 16871203
references.citation: Chem Rev. 2000 Mar 8;100(3):925-1024
references.pmid: 11749256
references.citation: Anal Chem. 1998 Aug 1;70(15):3123-30
references.pmid: 11013717
references.citation: Neuropharmacology. 2007 Jun;52(8):1596-605
references.pmid: 17459426
references.citation: Nature. 2013 Aug 29;500(7464):575-9
references.pmid: 23913271
references.citation: J Neurosci. 2010 Jun 16;30(24):8229-33
references.pmid: 20554874
references.citation: Anal Chem. 1998 Dec 1;70(23):4974-84
references.pmid: 21644679
references.citation: Anal Chem. 1996 Jun 1;68(11):359A-363A
references.pmid: 8686920
references.citation: Lab Chip. 2008 Jul;8(7):1048-55
references.pmid: 18584078
references.citation: Front Biosci (Elite Ed). 2013 Jan 01;5:249-57
references.pmid: 23276986
references.citation: Science. 2006 Mar 17;311(5767):1570-4
references.pmid: 16543451