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Fast Scan Cyclic Voltammetry to Assess Dopamine Function: From Circuits to Behavior

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Dopaminergic System Function and Dysfunction: Experimental Approaches

Part of the book series: Neuromethods ((NM,volume 193))

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Abstract

Electrochemical techniques have allowed investigators to measure analytes of interest for decades. Of these techniques, fast scan cyclic voltammetry (FSCV) offers advantages that make it ideal for applications in neuroscience research. FSCV is particularly valuable due to its high temporal resolution and specificity for analytes such as dopamine (DA), serotonin, and norepinephrine. Finally, the development of FSCV for use in anesthetized, ex vivo, and freely moving preparations has broadened experimental options—allowing investigators to measure DA across a wide range of contexts. In this chapter, we describe FSCV, its principles and methodologies, popular implementations, and provide examples of discoveries made with this powerful technique.

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References

  1. España RA, Oleson EB, Locke JL, Brookshire BR, Roberts DC, Jones SR (2010) The hypocretin-orexin system regulates cocaine self-administration via actions on the mesolimbic dopamine system. Eur J Neurosci 31(2):336–348. PMID20039943; PMC2881680

    Article  Google Scholar 

  2. Fordahl SC, Locke JL, Jones SR (2016) High fat diet augments amphetamine sensitization in mice: role of feeding pattern, obesity, and dopamine terminal changes. Neuropharmacology 109:170–182. PMID27267686; PMC4970886

    Article  CAS  Google Scholar 

  3. Gan JO, Walton ME, Phillips PE (2010) Dissociable cost and benefit encoding of future rewards by mesolimbic dopamine. Nat Neurosci 13(1):25–27. PMID19904261; PMC2800310

    Article  CAS  Google Scholar 

  4. Garris PA, Kilpatrick M, Bunin MA, Michael D, Walker QD, Wightman RM (1999) Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation. Nature 398(6722):67–69. PMID10078530

    Article  CAS  Google Scholar 

  5. Wightman RM, Kuhr WG, Ewing AG (1986) Voltammetric detection of dopamine release in the rat corpus striatum. Ann N Y Acad Sci 473:92–105. PMID3541742

    Article  CAS  Google Scholar 

  6. Aggarwal S, Liu X, Rice C, Menell P, Clark PJ, Paparoidamis N, Xiao YC, Salvino JM, Fontana ACK, España RA, Kortagere S, Mortensen OV (2019) Identification of a novel allosteric modulator of the human dopamine transporter. ACS Chem Neurosci 10(8):3718–3730. PMID31184115; PMC6703927

    Article  CAS  Google Scholar 

  7. Brodnik ZD, Black EM, Clark MJ, Kornsey KN, Snyder NW, España RA (2017) Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine. Neuropharmacology 125:295–307. PMID28778834; PMC5585061

    Article  CAS  Google Scholar 

  8. Calipari ES, Juarez B, Morel C, Walker DM, Cahill ME, Ribeiro E, Roman-Ortiz C, Ramakrishnan C, Deisseroth K, Han MH, Nestler EJ (2017) Dopaminergic dynamics underlying sex-specific cocaine reward. Nat Commun 8:13877. PMID28072417; PMC5234081

    Article  CAS  Google Scholar 

  9. Ferris MJ, España RA, Locke JL, Konstantopoulos JK, Rose JH, Chen R, Jones SR (2014) Dopamine transporters govern diurnal variation in extracellular dopamine tone. Proc Natl Acad Sci U S A 111(26):E2751–E2759. PMID24979798; PMC4084435

    Article  CAS  Google Scholar 

  10. Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80(1):1–27. PMID9658025

    Article  CAS  Google Scholar 

  11. Gainetdinov RR, Jones SR, Fumagalli F, Wightman RM, Caron MG (1998) Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis. Brain Res Brain Res Rev 26(2–3):148–153. PMID9651511

    Article  CAS  Google Scholar 

  12. Hamid AA, Frank MJ, Moore CI (2021) Wave-like dopamine dynamics as a mechanism for spatiotemporal credit assignment. Cell 184(10):2733–49.e16. PMID33861952; PMC8122079

    Article  CAS  Google Scholar 

  13. Jones SR, Gainetdinov RR, Hu XT, Cooper DC, Wightman RM, White FJ, Caron MG (1999) Loss of autoreceptor functions in mice lacking the dopamine transporter. Nat Neurosci 2(7):649–655. PMID10404198

    Article  CAS  Google Scholar 

  14. Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S (2002) Dopamine transport function is elevated in cocaine users. J Neurochem 81(2):292–300. PMID12064476

    Article  CAS  Google Scholar 

  15. Mohebi A, Pettibone JR, Hamid AA, Wong JT, Vinson LT, Patriarchi T, Tian L, Kennedy RT, Berke JD (2019) Dissociable dopamine dynamics for learning and motivation. Nature 570(7759):65–70. PMID31118513; PMC6555489

    Article  CAS  Google Scholar 

  16. Threlfell S, Lalic T, Platt NJ, Jennings KA, Deisseroth K, Cragg SJ (2012) Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons. Neuron 75(1):58–64. PMID22794260

    Article  CAS  Google Scholar 

  17. Zahniser NR, Sorkin A (2004) Rapid regulation of the dopamine transporter: role in stimulant addiction? Neuropharmacology 47(Suppl 1):80–91. PMID15464127

    Article  CAS  Google Scholar 

  18. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: burst firing. J Neurosci 4(11):2877–2890. PMID6150071; PMC6564720

    Article  CAS  Google Scholar 

  19. Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: single spike firing. J Neurosci 4(11):2866–2876. PMID6150070; PMC6564731

    Article  CAS  Google Scholar 

  20. Korotkova TM, Sergeeva OA, Eriksson KS, Haas HL, Brown RE (2003) Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci 23(1):7–11. PMID12514194; PMC6742159

    Article  CAS  Google Scholar 

  21. Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL (2008) Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition. J Neurosci 28(36):8908–8913. PMID18768684; PMC6670880

    Article  CAS  Google Scholar 

  22. Margolis EB, Lock H, Hjelmstad GO, Fields HL (2006) The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons? J Physiol 577(Pt 3):907–924. PMID16959856; PMC1890372

    Article  CAS  Google Scholar 

  23. Morris G, Nevet A, Arkadir D, Vaadia E, Bergman H (2006) Midbrain dopamine neurons encode decisions for future action. Nat Neurosci 9(8):1057–1063. PMID16862149

    Article  CAS  Google Scholar 

  24. Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275(5306):1593–1599

    Article  CAS  Google Scholar 

  25. Bocklisch C, Pascoli V, Wong JC, House DR, Yvon C, de Roo M, Tan KR, Luscher C (2013) Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science 341(6153):1521–1525. PMID24072923

    Article  CAS  Google Scholar 

  26. Gessa GL, Muntoni F, Collu M, Vargiu L, Mereu G (1985) Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res 348(1):201–203. PMID2998561

    Article  CAS  Google Scholar 

  27. Mereu G, Yoon KW, Boi V, Gessa GL, Naes L, Westfall TC (1987) Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine. Eur J Pharmacol 141(3):395–399. PMID3666033

    Article  CAS  Google Scholar 

  28. Del Castillo J, Katz B (1954) Statistical factors involved in neuromuscular facilitation and depression. J Physiol 124(3):574–585. PMID13175200; PMC1366293

    Article  Google Scholar 

  29. Katz B, Miledi R (1968) The role of calcium in neuromuscular facilitation. J Physiol 195(2):481–492. PMID4296699; PMC1351674

    Article  CAS  Google Scholar 

  30. Cummings DD, Wilcox KS, Dichter MA (1996) Calcium-dependent paired-pulse facilitation of miniature EPSC frequency accompanies depression of EPSCs at hippocampal synapses in culture. J Neurosci 16(17):5312–5323. PMID8757244; PMC6578891

    Article  CAS  Google Scholar 

  31. Debanne D, Guerineau NC, Gahwiler BH, Thompson SM (1996) Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J Physiol 491(Pt 1):163–176. PMID9011608; PMC1158767

    Article  CAS  Google Scholar 

  32. Nicola SM, Surmeier J, Malenka RC (2000) Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci 23:185–215. PMID10845063

    Article  CAS  Google Scholar 

  33. Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30(5):228–235. PMID17408758

    Article  CAS  Google Scholar 

  34. Marcott PF, Mamaligas AA, Ford CP (2014) Phasic dopamine release drives rapid activation of striatal D2-receptors. Neuron 84(1):164–176. PMID25242218; PMC4325987

    Article  CAS  Google Scholar 

  35. Schultz KN, Kennedy RT (2008) Time-resolved microdialysis for in vivo neurochemical measurements and other applications. Annu Rev Anal Chem (Palo Alto Calif) 1:627–661. PMID20636092

    Article  CAS  Google Scholar 

  36. Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology (Berl) 120(1):10–20. PMID7480530

    Article  CAS  Google Scholar 

  37. Gilinsky MA, Faibushevish AA, Lunte CE (2001) Determination of myocardial norepinephrine in freely moving rats using in vivo microdialysis sampling and liquid chromatography with dual-electrode amperometric detection. J Pharm Biomed Anal 24(5–6):929–935. PMID11248486; PMC2519812

    Article  CAS  Google Scholar 

  38. Shackman HM, Shou M, Cellar NA, Watson CJ, Kennedy RT (2007) Microdialysis coupled on-line to capillary liquid chromatography with tandem mass spectrometry for monitoring acetylcholine in vivo. J Neurosci Methods 159(1):86–92. PMID16876256

    Article  CAS  Google Scholar 

  39. Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE, Adhikari A, Lammel S, Mirzabekov JJ, Airan RD, Zalocusky KA, Tye KM, Anikeeva P, Malenka RC, Deisseroth K (2014) Natural neural projection dynamics underlying social behavior. Cell 157(7):1535–1551. PMID24949967; PMC4123133

    Article  CAS  Google Scholar 

  40. Patriarchi T, Cho JR, Merten K, Howe MW, Marley A, Xiong WH, Folk RW, Broussard GJ, Liang R, Jang MJ, Zhong H, Dombeck D, von Zastrow M, Nimmerjahn A, Gradinaru V, Williams JT, Tian L (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science 360(6396):eaat4422. PMID29853555; PMC6287765

    Article  Google Scholar 

  41. Sun F, Zeng J, Jing M, Zhou J, Feng J, Owen SF, Luo Y, Li F, Wang H, Yamaguchi T, Yong Z, Gao Y, Peng W, Wang L, Zhang S, Du J, Lin D, Xu M, Kreitzer AC, Cui G, Li Y (2018) A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell 174(2):481–96.e19. PMID30007419; PMC6092020

    Article  CAS  Google Scholar 

  42. Hawley MD, Tatawawadi SV, Piekarski S, Adams RN (1967) Electrochemical studies of the oxidation pathways of catecholamines. J Am Chem Soc 89(2):447–450. PMID6031636

    Article  CAS  Google Scholar 

  43. Kissinger PT, Hart JB, Adams RN (1973) Voltammetry in brain tissue--a new neurophysiological measurement. Brain Res 55(1):209–213. PMID4145914

    Article  CAS  Google Scholar 

  44. Millar J, Stamford JA, Kruk ZL, Wightman RM (1985) Electrochemical, pharmacological and electrophysiological evidence of rapid dopamine release and removal in the rat caudate nucleus following electrical stimulation of the median forebrain bundle. Eur J Pharmacol 109(3):341–348. PMID3872803

    Article  CAS  Google Scholar 

  45. McCreery RL (2008) Advanced carbon electrode materials for molecular electrochemistry. Chem Rev 108(7):2646–2687. PMID18557655

    Article  CAS  Google Scholar 

  46. Clark JJ, Sandberg SG, Wanat MJ, Gan JO, Horne EA, Hart AS, Akers CA, Parker JG, Willuhn I, Martinez V, Evans SB, Stella N, Phillips PE (2010) Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals. Nat Methods 7(2):126–129. PMID20037591; PMC2849934

    Article  CAS  Google Scholar 

  47. Brodnik ZD, Black EM, España RA (2020) Accelerated development of cocaine-associated dopamine transients and cocaine use vulnerability following traumatic stress. Neuropsychopharmacology 45(3):472–481. PMID31539899; PMC6969179

    Article  Google Scholar 

  48. Shaw JK, Ferris MJ, Locke JL, Brodnik ZD, Jones SR, España RA (2017) Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine. Addict Biol 22(6):1695–1705. PMID27480648; PMC5468487

    Article  CAS  Google Scholar 

  49. Albulbul A (2016) Evaluating major electrode types for idle biological signal measurements for modern medical technology. Bioengineering (Basel) 3(3):20. PMID28952582; PMC5597189

    Article  Google Scholar 

  50. Hashemi P, Walsh PL, Guillot TS, Gras-Najjar J, Takmakov P, Crews FT, Wightman RM (2011) Chronically implanted, Nafion-coated Ag/AgCl reference electrodes for neurochemical applications. ACS Chem Neurosci 2(11):658–666. PMID22125666; PMC3224088

    Article  CAS  Google Scholar 

  51. Moussy F, Harrison DJ, Rajotte RV (1994) A miniaturized Nafion-based glucose sensor: in vitro and in vivo evaluation in dogs. Int J Artif Organs 17(2):88–94. PMID8039946

    Article  CAS  Google Scholar 

  52. Phillips PE, Stuber GD, Heien ML, Wightman RM, Carelli RM (2003) Subsecond dopamine release promotes cocaine seeking. Nature 422(6932):614–618. PMID12687000

    Article  CAS  Google Scholar 

  53. Baur JE, Kristensen EW, May LJ, Wiedemann DJ, Wightman RM (1988) Fast-scan voltammetry of biogenic amines. Anal Chem 60(13):1268–1272. PMID3213946

    Article  CAS  Google Scholar 

  54. Ewing AG, Dayton MA, Wightman RM (1981) Pulse voltammetry with microvoltammetric electrodes. Anal Chem 53:1842–1847

    Article  CAS  Google Scholar 

  55. Kuhr WG, Ewing AG, Caudill WL, Wightman RM (1984) Monitoring the stimulated release of dopamine with in vivo voltammetry. I: Characterization of the response observed in the caudate nucleus of the rat. J Neurochem 43(2):560–569. PMID6736965

    Article  CAS  Google Scholar 

  56. Brodnik ZD, España RA (2015) Dopamine uptake dynamics are preserved under isoflurane anesthesia. Neurosci Lett 606:129–134

    Article  CAS  Google Scholar 

  57. Cid-Jofre V, Garate-Perez M, Clark PJ, Valero-Jara V, España RA, Sotomayor-Zarate R, Cruz G, Renard GM (2021) Chronic modafinil administration to preadolescent rats impairs social play behavior and dopaminergic system. Neuropharmacology 183:108404. PMID33197467

    Article  CAS  Google Scholar 

  58. Roberts JG, Sombers LA (2018) Fast-scan cyclic voltammetry: chemical sensing in the brain and beyond. Anal Chem 90(1):490–504. PMID29182309; PMC5750125

    Article  CAS  Google Scholar 

  59. Venton BJ, Cao Q (2020) Fundamentals of fast-scan cyclic voltammetry for dopamine detection. Analyst 145(4):1158–1168. PMID31922176; PMC7028514

    Article  CAS  Google Scholar 

  60. Qi L, Thomas E, White SH, Smith SK, Lee CA, Wilson LR, Sombers LA (2016) Unmasking the effects of L-DOPA on rapid dopamine signaling with an improved approach for Nafion coating carbon-fiber microelectrodes. Anal Chem 88(16):8129–8136. PMID27441547; PMC5226322

    Article  CAS  Google Scholar 

  61. Takmakov P, Zachek MK, Keithley RB, Walsh PL, Donley C, McCarty GS, Wightman RM (2010) Carbon microelectrodes with a renewable surface. Anal Chem 82(5):2020–2028. PMID20146453; PMC2838506

    Article  CAS  Google Scholar 

  62. Chang AY, Dutta G, Siddiqui S, Arumugam PU (2019) Surface fouling of ultrananocrystalline diamond microelectrodes during dopamine detection: improving lifetime via electrochemical cycling. ACS Chem Neurosci 10(1):313–322. PMID30285418

    Article  CAS  Google Scholar 

  63. Heien ML, Phillips PE, Stuber GD, Seipel AT, Wightman RM (2003) Overoxidation of carbon-fiber microelectrodes enhances dopamine adsorption and increases sensitivity. Analyst 128(12):1413–1419. PMID14737224

    Article  CAS  Google Scholar 

  64. Levy KA, Brodnik ZD, Shaw JK, Perrey DA, Zhang Y, España RA (2017) Hypocretin receptor 1 blockade produces bimodal modulation of cocaine-associated mesolimbic dopamine signaling. Psychopharmacology (Berl) 234(18):2761–2776. PMID28667509; PMC5709206

    Article  CAS  Google Scholar 

  65. Meunier CJ, Roberts JG, McCarty GS, Sombers LA (2017) Background signal as an in situ predictor of dopamine oxidation potential: improving interpretation of fast-scan cyclic voltammetry data. ACS Chem Neurosci 8(2):411–419. PMID28044445; PMC5684890

    Article  CAS  Google Scholar 

  66. Roberts JG, Toups JV, Eyualem E, McCarty GS, Sombers LA (2013) In situ electrode calibration strategy for voltammetric measurements in vivo. Anal Chem 85(23):11568–11575. PMID24224460; PMC3935327

    Article  CAS  Google Scholar 

  67. Alonso IP, Pino JA, Kortagere S, Torres GE, España RA (2021) Dopamine transporter function fluctuates across sleep/wake state: potential impact for addiction. Neuropsychopharmacology 46:699–708. PMID33032296

    Article  CAS  Google Scholar 

  68. Yorgason JT, España RA, Jones SR (2011) Demon voltammetry and analysis software: analysis of cocaine-induced alterations in dopamine signaling using multiple kinetic measures. J Neurosci Methods 202(2):158–164. PMID21392532; PMC3149733

    Article  CAS  Google Scholar 

  69. Covey DP, Bunner KD, Schuweiler DR, Cheer JF, Garris PA (2016) Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids. Eur J Neurosci 43(12):1661–1673. PMID27038339; PMC5819353

    Article  Google Scholar 

  70. Goodwin JS, Larson GA, Swant J, Sen N, Javitch JA, Zahniser NR, De Felice LJ, Khoshbouei H (2009) Amphetamine and methamphetamine differentially affect dopamine transporters in vitro and in vivo. J Biol Chem 284(5):2978–2989. PMID19047053; PMC2631950

    Article  CAS  Google Scholar 

  71. Kutlu MG, Brady LJ, Peck EG, Hofford RS, Yorgason JT, Siciliano CA, Kiraly DD, Calipari ES (2018) Granulocyte colony stimulating factor enhances reward learning through potentiation of mesolimbic dopamine system function. J Neurosci 38(41):8845–8859. PMID30150359; PMC6181308

    Article  CAS  Google Scholar 

  72. Wightman RM, Heien ML, Wassum KM, Sombers LA, Aragona BJ, Khan AS, Ariansen JL, Cheer JF, Phillips PE, Carelli RM (2007) Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens. Eur J Neurosci 26(7):2046–2054. PMID17868375

    Article  Google Scholar 

  73. Keithley RB, Heien ML, Wightman RM (2009) Multivariate concentration determination using principal component regression with residual analysis. Trends Analyt Chem 28(9):1127–1136. PMID20160977; PMC2760950

    Article  CAS  Google Scholar 

  74. Rodeberg NT, Johnson JA, Cameron CM, Saddoris MP, Carelli RM, Wightman RM (2015) Construction of training sets for valid calibration of in vivo cyclic voltammetric data by principal component analysis. Anal Chem 87(22):11484–11491. PMID26477708; PMC5131642

    Article  CAS  Google Scholar 

  75. Kuhr WG, Wightman RM (1986) Real-time measurement of dopamine release in rat brain. Brain Res 381(1):168–171. PMID3489505

    Article  CAS  Google Scholar 

  76. Wightman RM, May LJ, Michael AC (1988) Detection of dopamine dynamics in the brain. Anal Chem 60(13):769A–779A. PMID3063135

    Article  CAS  Google Scholar 

  77. Wightman RM, Zimmerman JB (1990) Control of dopamine extracellular concentration in rat striatum by impulse flow and uptake. Brain Res Brain Res Rev 15(2):135–144. PMID2282449

    Article  CAS  Google Scholar 

  78. Budygin EA, Phillips PE, Wightman RM, Jones SR (2001) Terminal effects of ethanol on dopamine dynamics in rat nucleus accumbens: an in vitro voltammetric study. Synapse 42(2):77–79. PMID11574942

    Article  CAS  Google Scholar 

  79. Park J, Takmakov P, Wightman RM (2011) In vivo comparison of norepinephrine and dopamine release in rat brain by simultaneous measurements with fast-scan cyclic voltammetry. J Neurochem 119(5):932–944. PMID21933188; PMC3217157

    Article  CAS  Google Scholar 

  80. Robinson DL, Venton BJ, Heien ML, Wightman RM (2003) Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo. Clin Chem 49(10):1763–1773. PMID14500617

    Article  CAS  Google Scholar 

  81. Stuber GD, Roitman MF, Phillips PE, Carelli RM, Wightman RM (2005) Rapid dopamine signaling in the nucleus accumbens during contingent and noncontingent cocaine administration. Neuropsychopharmacology 30(5):853–863. PMID15549053

    Article  CAS  Google Scholar 

  82. Garris PA, Ciolkowski EL, Pastore P, Wightman RM (1994) Efflux of dopamine from the synaptic cleft in the nucleus accumbens of the rat brain. J Neurosci 14(10):6084–6093. PMID7931564; PMC6577011

    Article  CAS  Google Scholar 

  83. Garris PA, Wightman RM (1995) Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and striatum of the rat in vivo. Synapse 20(3):269–279. PMID7570359

    Article  CAS  Google Scholar 

  84. May LJ, Wightman RM (1989) Heterogeneity of stimulated dopamine overflow within rat striatum as observed with in vivo voltammetry. Brain Res 487(2):311–320. PMID2786444

    Article  CAS  Google Scholar 

  85. Walker QD, Rooney MB, Wightman RM, Kuhn CM (2000) Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry. Neuroscience 95(4):1061–1070. PMID10682713

    Article  CAS  Google Scholar 

  86. Shaw JK, Pamela Alonso I, Lewandowski SI, Scott MO, O’Connor BM, Aggarwal S, De Biasi M, Mortensen OV, España RA (2021) Individual differences in dopamine uptake in the dorsomedial striatum prior to cocaine exposure predict motivation for cocaine in male rats. Neuropsychopharmacology 46(10):1757–1767. PMID33953341

    Article  CAS  Google Scholar 

  87. Kelly RS, Wightman RM (1987) Detection of dopamine overflow and diffusion with voltammetry in slices of rat brain. Brain Res 423(1–2):79–87. PMID3676822

    Article  CAS  Google Scholar 

  88. Brodnik ZD, Batra A, Oleson EB, España RA (2019) Local GABAA receptor-mediated suppression of dopamine release within the nucleus accumbens. ACS Chem Neurosci 10(4):1978–1985. PMID30253088

    Article  CAS  Google Scholar 

  89. Jones SR, Gainetdinov RR, Jaber M, Giros B, Wightman RM, Caron MG (1998) Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci U S A 95(7):4029–4034. PMID9520487; PMC19957

    Article  CAS  Google Scholar 

  90. Jones SR, Gainetdinov RR, Wightman RM, Caron MG (1998) Mechanisms of amphetamine action revealed in mice lacking the dopamine transporter. J Neurosci 18(6):1979–1986. PMID9482784; PMC6792915

    Article  CAS  Google Scholar 

  91. Schmitz Y, Schmauss C, Sulzer D (2002) Altered dopamine release and uptake kinetics in mice lacking D2 receptors. J Neurosci 22(18):8002–8009. PMID12223553; PMC6758092

    Article  CAS  Google Scholar 

  92. Brodnik ZD, Xu W, Batra A, Lewandowski SI, Ruiz CM, Mortensen OV, Kortagere S, Mahler SV, España RA (2020) Chemogenetic manipulation of dopamine neurons dictates cocaine potency at distal dopamine transporters. J Neurosci 40(45):8767–8779. PMID33046544; PMC7643298

    Article  CAS  Google Scholar 

  93. Jones SR, Bowman BP, Kuhn CM, Wightman RM (1996) Development of dopamine neurotransmission and uptake inhibition in the caudate nucleus as measured by fast-cyclic voltammetry. Synapse 24(3):305–307. PMID8923671

    Article  CAS  Google Scholar 

  94. Jones SR, Garris PA, Kilts CD, Wightman RM (1995) Comparison of dopamine uptake in the basolateral amygdaloid nucleus, caudate-putamen, and nucleus accumbens of the rat. J Neurochem 64(6):2581–2589. PMID7760038

    Article  CAS  Google Scholar 

  95. Anzalone A, Lizardi-Ortiz JE, Ramos M, De Mei C, Hopf FW, Iaccarino C, Halbout B, Jacobsen J, Kinoshita C, Welter M, Caron MG, Bonci A, Sulzer D, Borrelli E (2012) Dual control of dopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci 32(26):9023–9034. PMID22745501; PMC3752062

    Article  CAS  Google Scholar 

  96. Bello EP, Mateo Y, Gelman DM, Noain D, Shin JH, Low MJ, Alvarez VA, Lovinger DM, Rubinstein M (2011) Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nat Neurosci 14(8):1033–1038. PMID21743470; PMC3175737

    Article  CAS  Google Scholar 

  97. Kennedy RT, Jones SR, Wightman RM (1992) Dynamic observation of dopamine autoreceptor effects in rat striatal slices. J Neurochem 59(2):449–455. PMID1352798

    Article  CAS  Google Scholar 

  98. Calipari ES, Huggins KN, Mathews TA, Jones SR (2012) Conserved dorsal-ventral gradient of dopamine release and uptake rate in mice, rats and rhesus macaques. Neurochem Int 61(7):986–991. PMID22819794; PMC3593229

    Article  CAS  Google Scholar 

  99. Berke JD (2018) What does dopamine mean? Nat Neurosci 21(6):787–793. PMID29760524; PMC6358212

    Article  CAS  Google Scholar 

  100. Garris PA, Christensen JR, Rebec GV, Wightman RM (1997) Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats. J Neurochem 68(1):152–161. PMID8978721

    Article  CAS  Google Scholar 

  101. Robinson DL, Phillips PE, Budygin EA, Trafton BJ, Garris PA, Wightman RM (2001) Sub-second changes in accumbal dopamine during sexual behavior in male rats. Neuroreport 12(11):2549–2552. PMID11496146

    Article  CAS  Google Scholar 

  102. Zhang L, Doyon WM, Clark JJ, Phillips PE, Dani JA (2009) Controls of tonic and phasic dopamine transmission in the dorsal and ventral striatum. Mol Pharmacol 76(2):396–404. PMID19460877; PMC2713129

    Article  CAS  Google Scholar 

  103. Roberts JG, Lugo-Morales LZ, Loziuk PL, Sombers LA (2013) Real-time chemical measurements of dopamine release in the brain. Methods Mol Biol 964:275–294. PMID23296789; PMC5259961

    Article  CAS  Google Scholar 

  104. Cragg SJ, Hille CJ, Greenfield SA (2000) Dopamine release and uptake dynamics within nonhuman primate striatum in vitro. J Neurosci 20(21):8209–8217. PMID11050144; PMC6772736

    Article  CAS  Google Scholar 

  105. Siciliano CA, Calipari ES, Jones SR (2014) Amphetamine potency varies with dopamine uptake rate across striatal subregions. J Neurochem 131(3):348–355. PMID24988947; PMC4205180

    Article  CAS  Google Scholar 

  106. Yorgason JT, Calipari ES, Ferris MJ, Karkhanis AN, Fordahl SC, Weiner JL, Jones SR (2016) Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum. Neuropharmacology 101:471–479. PMID26525189; PMC4681685

    Article  CAS  Google Scholar 

  107. Brodnik ZD, Bernstein DL, Prince CD, España RA (2015) Hypocretin receptor 1 blockade preferentially reduces high effort responding for cocaine without promoting sleep. Behav Brain Res 291:377–384. PMID26049058; PMC4734652

    Article  CAS  Google Scholar 

  108. Shnitko TA, Robinson DL (2015) Regional variation in phasic dopamine release during alcohol and sucrose self-administration in rats. ACS Chem Neurosci 6(1):147–154. PMID25493956; PMC4304482

    Article  CAS  Google Scholar 

  109. Richardson NR, Roberts DCS (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66(1):1–11

    Article  CAS  Google Scholar 

  110. Borgland SL, Malenka RC, Bonci A (2004) Acute and chronic cocaine-induced potentiation of synaptic strength in the ventral tegmental area: electrophysiological and behavioral correlates in individual rats. J Neurosci 24(34):7482–7490. PMID15329395; PMC6729639

    Article  CAS  Google Scholar 

  111. Chen BT, Bowers MS, Martin M, Hopf FW, Guillory AM, Carelli RM, Chou JK, Bonci A (2008) Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA. Neuron 59(2):288–297. PMID18667156; PMC2593405

    Article  CAS  Google Scholar 

  112. Hurd YL, Ungerstedt U (1989) In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudate-putamen. Eur J Pharmacol 166(2):251–260. PMID2477259

    Article  CAS  Google Scholar 

  113. Kuczenski R, Segal DS, Aizenstein ML (1991) Amphetamine, cocaine, and fencamfamine: relationship between locomotor and stereotypy response profiles and caudate and accumbens dopamine dynamics. J Neurosci 11(9):2703–2712. PMID1715389; PMC6575248

    Article  CAS  Google Scholar 

  114. Moghaddam B, Bunney BS (1989) Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: comparison to amphetamine. Synapse 4(2):156–161. PMID2781466

    Article  CAS  Google Scholar 

  115. Weiss F, Paulus MP, Lorang MT, Koob GF (1992) Increases in extracellular dopamine in the nucleus accumbens by cocaine are inversely related to basal levels: effects of acute and repeated administration. J Neurosci 12(11):4372–4380. PMID1432099; PMC6576001

    Article  CAS  Google Scholar 

  116. Beuming T, Kniazeff J, Bergmann ML, Shi L, Gracia L, Raniszewska K, Newman AH, Javitch JA, Weinstein H, Gether U, Loland CJ (2008) The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nat Neurosci 11(7):780–789. PMID18568020; PMC2692229

    Article  CAS  Google Scholar 

  117. España RA, Roberts DC, Jones SR (2008) Short-acting cocaine and long-acting GBR-12909 both elicit rapid dopamine uptake inhibition following intravenous delivery. Neuroscience 155(1):250–257. PMID18597947; PMC2538802

    Article  Google Scholar 

  118. Mateo Y, Budygin EA, Morgan D, Roberts DC, Jones SR (2004) Fast onset of dopamine uptake inhibition by intravenous cocaine. Eur J Neurosci 20(10):2838–2842. PMID15548229

    Article  Google Scholar 

  119. Yorgason JT, Jones SR, España RA (2011) Low and high affinity dopamine transporter inhibitors block dopamine uptake within 5 sec of intravenous injection. Neuroscience 182:125–132. PMID21402130; PMC3085557

    Article  CAS  Google Scholar 

  120. Brodnik ZD, Ferris MJ, Jones SR, España RA (2017) Reinforcing doses of intravenous cocaine produce only modest dopamine uptake inhibition. ACS Chem Neurosci 8(2):281–289. PMID27936579; PMC5553220

    Article  CAS  Google Scholar 

  121. John CE, Jones SR (2007) Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices. Neuropharmacology 52(8):1596–1605. PMID17459426; PMC2041899

    Article  CAS  Google Scholar 

  122. Venton BJ, Seipel AT, Phillips PE, Wetsel WC, Gitler D, Greengard P, Augustine GJ, Wightman RM (2006) Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool. J Neurosci 26(12):3206–3209. PMID16554471; PMC6674099

    Article  CAS  Google Scholar 

  123. Siciliano CA, Fordahl SC, Jones SR (2016) Cocaine self-administration produces long-lasting alterations in dopamine transporter responses to cocaine. J Neurosci 36(30):7807–7816. PMID27466327; PMC4961771

    Article  CAS  Google Scholar 

  124. Kiyatkin EA, Kiyatkin DE, Rebec GV (2000) Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats. Neuroscience 98(4):729–741. PMID10891616

    Article  CAS  Google Scholar 

  125. Hart AS, Rutledge RB, Glimcher PW, Phillips PE (2014) Phasic dopamine release in the rat nucleus accumbens symmetrically encodes a reward prediction error term. J Neurosci 34(3):698–704. PMID24431428; PMC3891951

    Article  CAS  Google Scholar 

  126. Hamid AA, Pettibone JR, Mabrouk OS, Hetrick VL, Schmidt R, Vander Weele CM, Kennedy RT, Aragona BJ, Berke JD (2016) Mesolimbic dopamine signals the value of work. Nat Neurosci 19(1):117–126. PMID26595651; PMC4696912

    Article  CAS  Google Scholar 

  127. Calipari ES, Ferris MJ, Zimmer BA, Roberts DC, Jones SR (2013) Temporal pattern of cocaine intake determines tolerance vs sensitization of cocaine effects at the dopamine transporter. Neuropsychopharmacology 38(12):2385–2392. PMID23719505; PMC3799057

    Article  CAS  Google Scholar 

  128. Ferris MJ, Calipari ES, Mateo Y, Melchior JR, Roberts DC, Jones SR (2012) Cocaine self-administration produces pharmacodynamic tolerance: differential effects on the potency of dopamine transporter blockers, releasers, and methylphenidate. Neuropsychopharmacology 37(7):1708–1716. PMID22395730; PMC3358740

    Article  CAS  Google Scholar 

  129. Mateo Y, Lack CM, Morgan D, Roberts DC, Jones SR (2005) Reduced dopamine terminal function and insensitivity to cocaine following cocaine binge self-administration and deprivation. Neuropsychopharmacology 30(8):1455–1463. PMID15702135

    Article  CAS  Google Scholar 

  130. Addy NA, Daberkow DP, Ford JN, Garris PA, Wightman RM (2010) Sensitization of rapid dopamine signaling in the nucleus accumbens core and shell after repeated cocaine in rats. J Neurophysiol 104(2):922–931

    Article  CAS  Google Scholar 

  131. Calipari ES, Ferris MJ, Jones SR (2014) Extended access of cocaine self-administration results in tolerance to the dopamine-elevating and locomotor-stimulating effects of cocaine. J Neurochem 128(2):224–232. PMID24102293; PMC3947316

    Article  CAS  Google Scholar 

  132. Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37(4):577–582. PMID12597856

    Article  CAS  Google Scholar 

  133. Willuhn I, Burgeno LM, Groblewski PA, Phillips PE (2014) Excessive cocaine use results from decreased phasic dopamine signaling in the striatum. Nat Neurosci 17(5):704–709. PMID24705184; PMC4714770

    Article  CAS  Google Scholar 

  134. Willuhn I, Burgeno LM, Everitt BJ, Phillips PE (2012) Hierarchical recruitment of phasic dopamine signaling in the striatum during the progression of cocaine use. Proc Natl Acad Sci U S A 109(50):20703–20708. PMID23184975; PMC3528544

    Article  CAS  Google Scholar 

  135. Cheer JF, Aragona BJ, Heien ML, Seipel AT, Carelli RM, Wightman RM (2007) Coordinated accumbal dopamine release and neural activity drive goal-directed behavior. Neuron 54(2):237–244. PMID17442245

    Article  CAS  Google Scholar 

  136. Brodnik ZD, Alonso IP, Xu W, Zhang Y, Kortagere S, España RA (2020) Hypocretin receptor 1 involvement in cocaine-associated behavior: therapeutic potential and novel mechanistic insights. Brain Res 1731:145894. PMID30071195

    Article  CAS  Google Scholar 

  137. Challasivakanaka S, Zhen J, Smith ME, Reith MEA, Foster JD, Vaughan RA (2017) Dopamine transporter phosphorylation site threonine 53 is stimulated by amphetamines and regulates dopamine transport, efflux, and cocaine analog binding. J Biol Chem 292(46):19066–19075. PMID28939767; PMC5704487

    Article  CAS  Google Scholar 

  138. Foster JD, Yang JW, Moritz AE, Challasivakanaka S, Smith MA, Holy M, Wilebski K, Sitte HH, Vaughan RA (2012) Dopamine transporter phosphorylation site threonine 53 regulates substrate reuptake and amphetamine-stimulated efflux. J Biol Chem 287(35):29702–29712. PMID22722938; PMC3436161

    Article  CAS  Google Scholar 

  139. Schmitt KC, Reith ME (2010) Regulation of the dopamine transporter: aspects relevant to psychostimulant drugs of abuse. Ann N Y Acad Sci 1187:316–340. PMID20201860

    Article  CAS  Google Scholar 

  140. Bass CE, Grinevich VP, Vance ZB, Sullivan RP, Bonin KD, Budygin EA (2010) Optogenetic control of striatal dopamine release in rats. J Neurochem 114(5):1344–1352. PMID20534006; PMC2923233

    CAS  Google Scholar 

  141. Gompf HS, Budygin EA, Fuller PM, Bass CE (2015) Targeted genetic manipulations of neuronal subtypes using promoter-specific combinatorial AAVs in wild-type animals. Front Behav Neurosci 9:152. PMID26190981; PMC4488755

    Article  Google Scholar 

  142. Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K (2009) Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324(5930):1080–1084. PMID19389999; PMC5262197

    Article  CAS  Google Scholar 

  143. Van Bockstaele EJ, Pickel VM (1995) GABA-containing neurons in the ventral tegmental area project to the nucleus accumbens in rat brain. Brain Res 682(1–2):215–221. PMID7552315

    Article  Google Scholar 

  144. Melchior JR, Ferris MJ, Stuber GD, Riddle DR, Jones SR (2015) Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release. J Neurochem 134(5):833–844. PMID26011081; PMC4537642

    Article  CAS  Google Scholar 

  145. Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye KM, Janak PH, Deisseroth K (2011) Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Neuron 72(5):721–733. PMID22153370; PMC3282061

    Article  CAS  Google Scholar 

  146. Hynes TJ, Hrelja KM, Hathaway BA, Hounjet CD, Chernoff CS, Ebsary SA, Betts GD, Russell B, Ma L, Kaur S, Winstanley CA (2021) Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity. Addict Biol 26:e13022. PMID33559379

    Article  CAS  Google Scholar 

  147. Mahler SV, Brodnik ZD, Cox BM, Buchta WC, Bentzley BS, Quintanilla J, Cope ZA, Lin EC, Riedy MD, Scofield MD, Messinger J, Ruiz CM, Riegel AC, España RA, Aston-Jones G (2019) Chemogenetic manipulations of ventral tegmental area dopamine neurons reveal multifaceted roles in cocaine abuse. J Neurosci 39(3):503–518. PMID30446532; PMC6335749

    Article  CAS  Google Scholar 

  148. McElligott Z (2015) Optogenetic and chemogenetic approaches to advance monitoring molecules. ACS Chem Neurosci 6(7):944–947. PMID25791746

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Bethan M. O’Connor for expert technical assistance. This work was supported by NIH grants DA031900 and DA043787 to R.A.E.

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Authors and Affiliations

  1. Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA

    Philip J. Clark & Rodrigo A. España

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  1. Philip J. Clark
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  2. Rodrigo A. España
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Correspondence to Rodrigo A. España .

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  1. Escuela de Química y Farmacia y Centro Interdisciplinario de Neurociencia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago, Chile

    José Antonio Fuentealba-Evans

  2. Departamento de Anatomía Normal, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Pablo Henny

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Clark, P.J., España, R.A. (2023). Fast Scan Cyclic Voltammetry to Assess Dopamine Function: From Circuits to Behavior. In: Fuentealba-Evans, J.A., Henny, P. (eds) Dopaminergic System Function and Dysfunction: Experimental Approaches. Neuromethods, vol 193. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2799-0_11

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  • DOI: https://doi.org/10.1007/978-1-0716-2799-0_11

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