Advertisement

pp 1-33 | Cite as

Molecular Mechanisms of Amphetamines

  • Maarten E. A. ReithEmail author
  • Margaret E. Gnegy
Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

There is a plethora of amphetamine derivatives exerting stimulant, euphoric, anti-fatigue, and hallucinogenic effects; all structural properties allowing these effects are contained within the amphetamine structure. In the first part of this review, the interaction of amphetamine with the dopamine transporter (DAT), crucially involved in its behavioral effects, is covered, as well as the role of dopamine synthesis, the vesicular monoamine transporter VMAT2, and organic cation 3 transporter (OCT3). The second part deals with requirements in amphetamine’s effect on the kinases PKC, CaMKII, and ERK, whereas the third part focuses on where we are in developing anti-amphetamine therapeutics. Thus, treatments are discussed that target DAT, VMAT2, PKC, CaMKII, and OCT3. As is generally true for the development of therapeutics for substance use disorder, there are multiple preclinically promising specific compounds against (meth)amphetamine, for which further development and clinical trials are badly needed.

Keywords

Amphetamine use disorder Catecholamine Dopamine Monoamine transporter Neurotransmitter release Protein kinase 

Notes

Acknowledgments

The most recent work by the authors described in this review was supported by NIH DA 019676 (MEAR) and R01DA011697 (MEG). We are grateful for the input given on Sect. 4.1 by Kyle C. Schmitt.

References

  1. Alper KR, Lotsof HS, Kaplan CD (2008) The ibogaine medical subculture. J Ethnopharmacol 115:9–24Google Scholar
  2. Altshuler R, Gnegy M, Jutkiewicz E (2016) The protein kinase Cbeta inhibitor, enzastaurin, decreases amphetamine-stimulated behaviors in rats. FASEB J 30:1183–1188Google Scholar
  3. Anderson AL, Li SH, Markova D, Holmes TH, Chiang N, Kahn R, Campbell J, Dickerson DL, Galloway GP, Haning W, Roache JD, Stock C, Elkashef AM (2015) Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend 150:170–174Google Scholar
  4. Apel ED, Byford MF, Au D, Walsh KA, Storm DR (1990) Identification of the protein kinase C phosphorylation site in neuromodulin. Biochemistry 29:2330–2335Google Scholar
  5. Arnold EB, Molinoff PB, Rutledge CO (1977) The release of endogenous norepinephrine and dopamine from cerebral cortex by amphetamine. J Pharmacol Exp Ther 202:544–557Google Scholar
  6. Avelar AJ, Juliano SA, Garris PA (2013) Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms. J Neurochem 125:373–385Google Scholar
  7. Baldessarini RJ, Vogt M (1971) The uptake and subcellular distribution of aromatic amines in the brain of the rat. J Neurochem 18:2519–2533Google Scholar
  8. Banks ML, Blough BE, Fennell TR, Snyder RW, Negus SS (2013a) Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys. Neuropsychopharmacology 38:2698–2707Google Scholar
  9. Banks ML, Blough BE, Negus SS (2013b) Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys. Neuropsychopharmacology 38:395–404Google Scholar
  10. Banks ML, Smith DA, Blough BE (2016) Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys. Behav Pharmacol 27:196–203Google Scholar
  11. Beerepoot P, Lam VM, Salahpour A (2016) Pharmacological chaperones of the dopamine transporter rescue dopamine transporter deficiency syndrome mutations in heterologous cells. J Biol Chem 291:22053–22062Google Scholar
  12. Berfield JL, Wang LC, Reith ME (1999) Which form of dopamine is the substrate for the human dopamine transporter: the cationic or the uncharged species? J Biol Chem 274:4876–4882Google Scholar
  13. Bhat S, Hasenhuetl PS, Kasture A, El-Kasaby A, Baumann MH, Blough BE, Sucic S, Sandtner W, Freissmuth M (2017) Conformational state interactions provide clues to the pharmacochaperone potential of serotonin transporter partial substrates. J Biol Chem 292:16773–16786Google Scholar
  14. Brensilver M, Heinzerling KG, Shoptaw S (2013) Pharmacotherapy of amphetamine-type stimulant dependence: an update. Drug Alcohol Rev 32:449–460Google Scholar
  15. Browman KE, Kantor L, Richardson S, Badiani A, Robinson TE, Gnegy ME (1998) Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies. Brain Res 814:112–119Google Scholar
  16. Brown TK, Alper K (2018) Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. Am J Drug Alcohol Abuse 44:24–36Google Scholar
  17. Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W (2012) The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J Biol Chem 287:18524–18534Google Scholar
  18. Butcher SP, Fairbrother IS, Kelly JS, Arbuthnott GW (1988) Amphetamine-induced dopamine release in the rat striatum: an in vivo microdialysis study. J Neurochem 50:346–355Google Scholar
  19. Cadoni C, Pinna A, Russi G, Consolo S, Di Chiara G (1995) Role of vesicular dopamine in the in vivo stimulation of striatal dopamine transmission by amphetamine: evidence from microdialysis and Fos immunohistochemistry. Neuroscience 65:1027–1039Google Scholar
  20. Calipari ES, Ferris MJ (2013) Amphetamine mechanisms and actions at the dopamine terminal revisited. J Neurosci 33:8923–8925Google Scholar
  21. Cameron KN, Solis E Jr, Ruchala I, De Felice LJ, Eltit JM (2015) Amphetamine activates calcium channels through dopamine transporter-mediated depolarization. Cell Calcium 58:457–466Google Scholar
  22. Carlsson A, Fuxe K, Hamberger B, Lindqvist M (1966) Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons. Acta Physiol Scand 67:481–497Google Scholar
  23. Carpenter C, Sorenson RJ, Jin Y, Klossowski S, Cierpicki T, Gnegy M, Showalter HD (2016) Design and synthesis of triarylacrylonitrile analogues of tamoxifen with improved binding selectivity to protein kinase C. Bioorg Med Chem 24:5495–5504Google Scholar
  24. Carpenter C, Zestos AG, Altshuler R, Sorenson RJ, Guptaroy B, Showalter HD, Kennedy RT, Jutkiewicz E, Gnegy ME (2017) Direct and systemic administration of a CNS-permeant tamoxifen analog reduces amphetamine-induced dopamine release and reinforcing effects. Neuropsychopharmacology 42:1940–1949Google Scholar
  25. Carson DS, Taylor ER (2014) Commentary on Heinzerling et al. (2014): a growing methamphetamine dependence therapeutics graveyard. Addiction 109:1887–1888Google Scholar
  26. Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remiao F, Carvalho F, Bastos Mde L (2012) Toxicity of amphetamines: an update. Arch Toxicol 86:1167–1231Google Scholar
  27. Carvelli L, McDonald PW, Blakely RD, DeFelice LJ (2004) Dopamine transporters depolarize neurons by a channel mechanism. Proc Natl Acad Sci U S A 101:16046–16051Google Scholar
  28. Cervinski MA, Foster JD, Vaughan RA (2005) Psychoactive substrates stimulate dopamine transporter phosphorylation and down-regulation by cocaine-sensitive and protein kinase C-dependent mechanisms. J Biol Chem 280:40442–40449Google Scholar
  29. 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 292:19066–19075Google Scholar
  30. Chen N, Reith ME (2004) Interaction between dopamine and its transporter: role of intracellular sodium ions and membrane potential. J Neurochem 89:750–765Google Scholar
  31. Chen N, Reith ME (2008) Substrates dissociate dopamine transporter oligomers. J Neurochem 105:910–920Google Scholar
  32. Chen N, Vaughan RA, Reith ME (2001) The role of conserved tryptophan and acidic residues in the human dopamine transporter as characterized by site-directed mutagenesis. J Neurochem 77:1116–1127Google Scholar
  33. Chen N, Rickey J, Reith ME (2003) Na+ stimulates binding of dopamine to the dopamine transporter in cells but not in cell-free preparations. J Neurochem 86:678–686Google Scholar
  34. Chen N, Rickey J, Berfield JL, Reith ME (2004a) Aspartate 345 of the dopamine transporter is critical for conformational changes in substrate translocation and cocaine binding. J Biol Chem 279:5508–5519Google Scholar
  35. Chen N, Zhen J, Reith ME (2004b) Mutation of Trp84 and Asp313 of the dopamine transporter reveals similar mode of binding interaction for GBR12909 and benztropine as opposed to cocaine. J Neurochem 89:853–864Google Scholar
  36. Chen R, Furman CA, Zhang M, Kim MN, RWt G, Leitges M, Gnegy ME (2009) Protein kinase Cbeta is a critical regulator of dopamine transporter trafficking and regulates the behavioral response to amphetamine in mice. J Pharmacol Exp Ther 328:912–920Google Scholar
  37. Chico LK, van Eldik LJ, Watterson DM (2009) Targeting protein kinases in central nervous system disorders. Nat Rev Drug Discov 8:892–909Google Scholar
  38. Chiueh CC, Moore KE (1975) D-amphetamine-induced release of “newly synthesized” and “stored” dopamine from the caudate nucleus in vivo. J Pharmacol Exp Ther 192:642–653Google Scholar
  39. Corera AT, Costentin J, Bonnet JJ (2000) Binding of uptake blockers to the neuronal dopamine transporter: further investigation about cationic and anionic requirements. Naunyn Schmiedeberg’s Arch Pharmacol 362:213–221Google Scholar
  40. Covey DP, Juliano SA, Garris PA (2013) Amphetamine elicits opposing actions on readily releasable and reserve pools for dopamine. PLoS One 8:e60763Google Scholar
  41. Cubeddu LX, Lovenberg TW, Hoffman IS, Talmaciu RK (1989) Phorbol esters and D2-dopamine receptors. J Pharmacol Exp Ther 251:687–693Google Scholar
  42. Czoty PW, Blough BE, Fennell TR, Snyder RW, Nader MA (2016) Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys. Neuroscience 324:367–376Google Scholar
  43. Daberkow DP, Brown HD, Bunner KD, Kraniotis SA, Doellman MA, Ragozzino ME, Garris PA, Roitman MF (2013) Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. J Neurosci 33:452–463Google Scholar
  44. Dwoskin LP, Crooks PA (2002) A novel mechanism of action and potential use for lobeline as a treatment for psychostimulant abuse. Biochem Pharmacol 63:89–98Google Scholar
  45. Edashige K, Sato EF, Akimaru K, Yoshioka T, Utsumi K (1991) Nonsteroidal antiestrogen suppresses protein kinase C – its inhibitory effect on interaction of substrate protein with membrane. Cell Struct Funct 16:273–281Google Scholar
  46. Egana LA, Cuevas RA, Baust TB, Parra LA, Leak RK, Hochendoner S, Pena K, Quiroz M, Hong WC, Dorostkar MM, Janz R, Sitte HH, Torres GE (2009) Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3. J Neurosci 29:4592–4604Google Scholar
  47. Einat H, Yuan P, Szabo ST, Dogra S, Manji HK (2007) Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology 55:123–131Google Scholar
  48. Erreger K, Grewer C, Javitch JA, Galli A (2008) Currents in response to rapid concentration jumps of amphetamine uncover novel aspects of human dopamine transporter function. J Neurosci 28:976–989Google Scholar
  49. Eshleman AJ, Henningsen RA, Neve KA, Janowsky A (1994) Release of dopamine via the human transporter. Mol Pharmacol 45:312–316Google Scholar
  50. Fischer JF, Cho AK (1979) Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model. J Pharmacol Exp Ther 208:203–209Google Scholar
  51. Floor E, Meng L (1996) Amphetamine releases dopamine from synaptic vesicles by dual mechanisms. Neurosci Lett 215:53–56Google Scholar
  52. Fog JU, Khoshbouei H, Holy M, Owens WA, Vaegter CB, Sen N, Nikandrova Y, Bowton E, McMahon DG, Colbran RJ, Daws LC, Sitte HH, Javitch JA, Galli A, Gether U (2006) Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport. Neuron 51:417–429Google Scholar
  53. Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH (1997) Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 19:1271–1283Google Scholar
  54. Foster JD, Vaughan RA (2017) Phosphorylation mechanisms in dopamine transporter regulation. J Chem Neuroanat 83-84:10–18Google Scholar
  55. Foster JD, Pananusorn B, Vaughan RA (2002) Dopamine transporters are phosphorylated on N-terminal serines in rat striatum. J Biol Chem 277:25178–25186Google Scholar
  56. 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 287:29702–29712Google Scholar
  57. Freyberg Z, Sonders MS, Aguilar JI, Hiranita T, Karam CS, Flores J, Pizzo AB, Zhang Y, Farino ZJ, Chen A, Martin CA, Kopajtic TA, Fei H, Hu G, Lin YY, Mosharov EV, McCabe BD, Freyberg R, Wimalasena K, Hsin LW, Sames D, Krantz DE, Katz JL, Sulzer D, Javitch JA (2016) Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat Commun 7:10652Google Scholar
  58. Fudala PJ, Iwamoto ET (1986) Further studies on nicotine-induced conditioned place preference in the rat. Pharmacol Biochem Behav 25:1041–1049Google Scholar
  59. Furman CA, Chen R, Guptaroy B, Zhang M, Holz RW, Gnegy M (2009) Dopamine and amphetamine rapidly increase dopamine transporter trafficking to the surface: live-cell imaging using total internal reflection fluorescence microscopy. J Neurosci 29:3328–3336Google Scholar
  60. Garcia-Pardo MP, Roger-Sanchez C, Rodriguez-Arias M, Minarro J, Aguilar MA (2016) Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates. Eur J Pharmacol 781:10–24Google Scholar
  61. Gasser PJ (2019) Roles for the uptake2 transporter OCT3 in regulation of dopaminergic neurotransmission and behavior. Neurochem Int 123:46–49Google Scholar
  62. German DC, McMillen BA, Sanghera MK, Saffer SI, Shore PA (1981) Effects of severe dopamine depletion on dopamine neuronal impulse flow and on tyrosine hydroxylase regulation. Brain Res Bull 6:131–134Google Scholar
  63. Giambalvo CT (1992a) Protein kinase C and dopamine transport – 1. Effects of amphetamine in vivo. Neuropharmacology 31:1201–1210Google Scholar
  64. Giambalvo CT (1992b) Protein kinase C and dopamine transport – 2. Effects of amphetamine in vitro. Neuropharmacology 31:1211–1222Google Scholar
  65. Giambalvo CT (2003) Differential effects of amphetamine transport vs. dopamine reverse transport on particulate PKC activity in striatal synaptoneurosomes. Synapse 49:125–133Google Scholar
  66. Giambalvo CT (2004) Mechanisms underlying the effects of amphetamine on particulate PKC activity. Synapse 51:128–139Google Scholar
  67. Gnegy ME (2003) The effect of phosphorylation on amphetamine-mediated outward transport. Eur J Pharmacol 479:83–91Google Scholar
  68. Gnegy ME, Khoshbouei H, Berg KA, Javitch JA, Clarke WP, Zhang M, Galli A (2004) Intracellular Ca2+ regulates amphetamine-induced dopamine efflux and currents mediated by the human dopamine transporter. Mol Pharmacol 66:137–143Google Scholar
  69. Gonzalez AM, Walther D, Pazos A, Uhl GR (1994) Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res 22:219–226Google 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 284:2978–2989Google Scholar
  71. Granas C, Ferrer J, Loland CJ, Javitch JA, Gether U (2003) N-terminal truncation of the dopamine transporter abolishes phorbol ester- and substance P receptor-stimulated phosphorylation without impairing transporter internalization. J Biol Chem 278:4990–5000Google Scholar
  72. Gulley JM, Zahniser NR (2003) Rapid regulation of dopamine transporter function by substrates, blockers and presynaptic receptor ligands. Eur J Pharmacol 479:139–152Google Scholar
  73. Gundimeda U, Chen Z-H, Gopalakrishna R (1996) Tamoxifen modulates protein kinase C via oxidative stress in estrogen receptor-negative breast cancer cells. J Biol Chem 271:13504–13514Google Scholar
  74. Hadlock GC, Nelson CC, Baucum AJ 2nd, Hanson GR, Fleckenstein AE (2011) Ex vivo identification of protein-protein interactions involving the dopamine transporter. J Neurosci Methods 196:303–307Google Scholar
  75. Hamilton PJ, Belovich AN, Khelashvili G, Saunders C, Erreger K, Javitch JA, Sitte HH, Weinstein H, Matthies HJG, Galli A (2014) PIP2 regulates psychostimulant behaviors through its interaction with a membrane protein. Nat Chem Biol 10:582–589Google Scholar
  76. Harrod SB, Dwoskin LP, Crooks PA, Klebaur JE, Bardo MT (2001) Lobeline attenuates d-methamphetamine self-administration in rats. J Pharmacol Exp Ther 298:172–179Google Scholar
  77. Harrod SB, Dwoskin LP, Green TA, Gehrke BJ, Bardo MT (2003) Lobeline does not serve as a reinforcer in rats. Psychopharmacology 165:397–404Google Scholar
  78. Hastrup H, Karlin A, Javitch JA (2001) Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment. Proc Natl Acad Sci U S A 98:10055–10060Google Scholar
  79. Heikkila RE, Orlansky H, Cohen G (1975) Studies on the distinction between uptake inhibition and release of (3H)dopamine in rat brain tissue slices. Biochem Pharmacol 24:847–852Google Scholar
  80. Heinzerling KG, Swanson AN, Hall TM, Yi Y, Wu Y, Shoptaw SJ (2014) Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use. Addiction 109:1878–1886Google Scholar
  81. Herman M, Nagler SH (1954) Psychoses due to amphetamine. J Nerv Ment Dis 120:268–272Google Scholar
  82. Holz RW, Coyle JT (1974) The effects of various salts, temperature, and the alkaloids veratridine and batrachotoxin on the uptake of [3H] dopamine into synaptosomes from rat striatum. Mol Pharmacol 10:746–758Google Scholar
  83. Horton RE, Apple DM, Owens WA, Baganz NL, Cano S, Mitchell NC, Vitela M, Gould GG, Koek W, Daws LC (2013) Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression. J Neurosci 33:10534–10543Google Scholar
  84. Howell LL, Negus SS (2014) Monoamine transporter inhibitors and substrates as treatments for stimulant abuse. Adv Pharmacol 69:129–176Google Scholar
  85. Humphreys CJ, Wall SC, Rudnick G (1994) Ligand binding to the serotonin transporter: equilibria, kinetics, and ion dependence. Biochemistry 33:9118–9125Google Scholar
  86. Hurd YL, Ungerstedt U (1989) In vivo neurochemical profile of dopamine uptake inhibitors and releasers in rat caudate-putamen. Eur J Pharmacol 166:251–260Google Scholar
  87. Iversen L (2006) Neurotransmitter transporters and their impact on the development of psychopharmacology. Br J Pharmacol 147(Suppl 1):S82–S88Google Scholar
  88. Iwata S, Hewlett GH, Ferrell ST, Czernik AJ, Meiri KF, Gnegy ME (1996) Increased in vivo phosphorylation state of neuromodulin and synapsin I in striatum from rats treated with repeated amphetamine. J Pharmacol Exp Ther 278:1428–1434Google Scholar
  89. Iwata S, Hewlett GH, Gnegy ME (1997) Amphetamine increases the phosphorylation of neuromodulin and synapsin I in rat striatal synaptosomes. Synapse 26:281–291Google Scholar
  90. Jacobs MT, Zhang YW, Campbell SD, Rudnick G (2007) Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. J Biol Chem 282:29441–29447Google Scholar
  91. Jardetzky O (1966) Simple allosteric model for membrane pumps. Nature 211:969–970Google Scholar
  92. Johnson J, Milner G (1966) Psychiatric complications of amphetamine substances. Acta Psychiatr Scand 42:252–263Google Scholar
  93. Johnson LA, Furman CA, Zhang M, Guptaroy B, Gnegy ME (2005a) Rapid delivery of the dopamine transporter to the plasmalemmal membrane upon amphetamine stimulation. Neuropharmacology 49:750–758Google Scholar
  94. Johnson LA, Guptaroy B, Lund D, Shamban S, Gnegy ME (2005b) Regulation of amphetamine-stimulated dopamine efflux by protein kinase C beta. J Biol Chem 280:10914–10919Google Scholar
  95. Jones SR, Gainetdinov RR, Wightman RM, Caron MG (1998) Mechanisms of amphetamine action revealed in mice lacking the dopamine transporter. J Neurosci 18:1979–1986Google Scholar
  96. Jones SR, Joseph JD, Barak LS, Caron MG, Wightman RM (1999) Dopamine neuronal transport kinetics and effects of amphetamine. J Neurochem 73:2406–2414Google Scholar
  97. Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A (2005) Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci U S A 102:3495–3500Google Scholar
  98. Kangiser MM, Dwoskin LP, Zheng G, Crooks PA, Stairs DJ (2018) Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats. Behav Pharmacol 29:87–97Google Scholar
  99. Kantor L, Gnegy ME (1998) Protein kinase C inhibitors block amphetamine-mediated dopamine release in rat striatal slices. J Pharmacol Exp Ther 284:592–598Google Scholar
  100. Kantor L, Hewlett GH, Gnegy ME (1999) Enhanced amphetamine- and K+-mediated dopamine release in rat striatum after repeated amphetamine: differential requirements for Ca2+- and calmodulin-dependent phosphorylation and synaptic vesicles. J Neurosci 19:3801–3808Google Scholar
  101. Kantor L, Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME (2001) Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells. J Pharmacol Exp Ther 297:1016–1024Google Scholar
  102. Karam CS, Sen N, Javitch JA (2017) Phospho-specific antibodies targeting the amino terminus of the human dopamine transporter. J Chem Neuroanat 83-84:91–98Google Scholar
  103. Katz JL, Izenwasser S, Kline RH, Allen AC, Newman AH (1999) Novel 3alpha-diphenylmethoxytropane analogs: selective dopamine uptake inhibitors with behavioral effects distinct from those of cocaine. J Pharmacol Exp Ther 288:302–315Google Scholar
  104. Khoshbouei H, Wang H, Lechleiter JD, Javitch JA, Galli A (2003) Amphetamine-induced dopamine efflux. A voltage-sensitive and intracellular Na+-dependent mechanism. J Biol Chem 278:12070–12077Google Scholar
  105. Khoshbouei H, Sen N, Guptaroy B, Johnson L, Lund D, Gnegy ME, Galli A, Javitch JA (2004) N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux. PLoS Biol 2:E78Google Scholar
  106. King M, Hosmer H, Dresbach M (1928) Physiological reactions induced by alpha-lobeline. I. Intravenous injections during anesthesia and certain other forms of depression. J Pharmacol Exp Ther 32:241–272Google Scholar
  107. Krishnamurthy H, Gouaux E (2012) X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481:469–474Google Scholar
  108. Kuhr WG, Ewing AG, Near JA, Wightman RM (1985) Amphetamine attenuates the stimulated release of dopamine in vivo. J Pharmacol Exp Ther 232:388–394Google Scholar
  109. Lee AM, Messing RO (2008) Protein kinases and addiction. Ann N Y Acad Sci 1141:22–57Google Scholar
  110. Lee NK, Jenner L, Harney A, Cameron J (2018a) Pharmacotherapy for amphetamine dependence: a systematic review. Drug Alcohol Depend 191:309–337Google Scholar
  111. Lee NR, Zheng G, Crooks PA, Bardo MT, Dwoskin LP (2018b) New scaffold for lead compounds to treat methamphetamine use disorders. AAPS J 20:29Google Scholar
  112. Lentzen H, Philippu A (1981) Physico-chemical properties of phenethylamines and their uptake into synaptic vesicles of the caudate nucleus. Biochem Pharmacol 30:1759–1764Google Scholar
  113. Leviel V (2011) Dopamine release mediated by the dopamine transporter, facts and consequences. J Neurochem 118:475–489Google Scholar
  114. Li LB, Reith ME (1999) Modeling of the interaction of Na+ and K+ with the binding of dopamine and [3H]WIN 35,428 to the human dopamine transporter. J Neurochem 72:1095–1109Google Scholar
  115. Li LB, Reith ME (2000) Interaction of Na+, K+, and Cl- with the binding of amphetamine, octopamine, and tyramine to the human dopamine transporter. J Neurochem 74:1538–1552Google Scholar
  116. Li LB, Cui XN, Reith MA (2002) Is Na(+) required for the binding of dopamine, amphetamine, tyramine, and octopamine to the human dopamine transporter? Naunyn Schmiedeberg’s Arch Pharmacol 365:303–311Google Scholar
  117. Li Y, Cheng SY, Chen N, Reith ME (2010) Interrelation of dopamine transporter oligomerization and surface presence as studied with mutant transporter proteins and amphetamine. J Neurochem 114:873–885Google Scholar
  118. Liang NY, Rutledge CO (1982) Evidence for carrier-mediated efflux of dopamine from corpus striatum. Biochem Pharmacol 31:2479–2484Google Scholar
  119. Lien EA, Solheim E, Ueland PM (1991) Distribution of tamoxifen and its metabolites in rat and human tissues during steady-state treatment. Cancer Res 51:4837–4844Google Scholar
  120. Lightman SL, Iversen LL (1969) The role of uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart. Br J Pharmacol 37:638–649Google Scholar
  121. Lin M, Sambo D, Khoshbouei H (2016) Methamphetamine regulation of firing activity of dopamine neurons. J Neurosci 36:10376–10391Google Scholar
  122. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, Kopajtic T, Shi L, Katz JL, Tanda G, Newman AH (2012) R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry 72:405–413Google Scholar
  123. Loweth JA, Baker LK, Guptaa T, Guillory AM, Vezina P (2008) Inhibition of CaMKII in the nucleus accumbens shell decreases enhanced amphetamine intake in sensitized rats. Neurosci Lett 444:157–160Google Scholar
  124. Loweth JA, Svoboda R, Austin JD, Guillory AM, Vezina P (2009) The PKC inhibitor Ro31-8220 blocks acute amphetamine-induced dopamine overflow in the nucleus accumbens. Neurosci Lett 455:88–92Google Scholar
  125. Loweth JA, Singer BF, Baker LK, Wilke G, Inamine H, Bubula N, Alexander JK, Carlezon WA Jr, Neve RL, Vezina P (2010) Transient overexpression of alpha-Ca2+/calmodulin-dependent protein kinase II in the nucleus accumbens shell enhances behavioral responding to amphetamine. J Neurosci 30:939–949Google Scholar
  126. Luderman KD, Chen R, Ferris MJ, Jones SR, Gnegy ME (2015) Protein kinase C beta regulates the D(2)-like dopamine autoreceptor. Neuropharmacology 89:335–341Google Scholar
  127. Malcolm E, Carroll FI, Blough B, Damaj MI, Shoaib M (2015) Examination of the metabolite hydroxybupropion in the reinforcing and aversive stimulus effects of nicotine in rats. Psychopharmacology 232:2763–2771Google Scholar
  128. Malinauskaite L, Quick M, Reinhard L, Lyons JA, Yano H, Javitch JA, Nissen P (2014) A mechanism for intracellular release of Na+ by neurotransmitter/sodium symporters. Nat Struct Mol Biol 21:1006–1012Google Scholar
  129. Mayer FP, Luf A, Nagy C, Holy M, Schmid R, Freissmuth M, Sitte HH (2017) Application of a combined approach to identify new psychoactive street drugs and decipher their mechanisms at monoamine transporters. Curr Top Behav Neurosci 32:333–350Google Scholar
  130. Mayer FP, Schmid D, Owens WA, Gould GG, Apuschkin M, Kudlacek O, Salzer I, Boehm S, Chiba P, Williams PH, Wu HH, Gether U, Koek W, Daws LC, Sitte HH (2018) An unsuspected role for organic cation transporter 3 in the actions of amphetamine. Neuropsychopharmacology 43:2408–2417Google Scholar
  131. Meinild AK, Sitte HH, Gether U (2004) Zinc potentiates an uncoupled anion conductance associated with the dopamine transporter. J Biol Chem 279:49671–49679Google Scholar
  132. Meiri KF, Bickerstaff LE, Schwob JE (1991) Monoclonal antibodies show that kinase C phosphorylation of GAP-43 during axonogenesis is both spatially and temporally restricted in vivo. J Cell Biol 112:991–1005Google Scholar
  133. Meyer AC, Horton DB, Neugebauer NM, Wooters TE, Nickell JR, Dwoskin LP, Bardo MT (2011) Tetrabenazine inhibition of monoamine uptake and methamphetamine behavioral effects: locomotor activity, drug discrimination and self-administration. Neuropharmacology 61:849–856Google Scholar
  134. Mikelman S, Mardirossian N, Gnegy ME (2017a) Tamoxifen and amphetamine abuse: are there therapeutic possibilities? J Chem Neuroanat 83-84:50–58Google Scholar
  135. Mikelman SR, Guptaroy B, Gnegy ME (2017b) Tamoxifen and its active metabolites inhibit dopamine transporter function independently of the estrogen receptors. J Neurochem 141:31–36Google Scholar
  136. Mikelman SR, Guptaroy B, Schmitt KC, Jones KT, Zhen J, Reith MEA, Gnegy ME (2018) Tamoxifen directly interacts with the dopamine transporter. J Pharmacol Exp Ther 367:119–128Google Scholar
  137. Mundorf ML, Hochstetler SE, Wightman RM (1999) Amine weak bases disrupt vesicular storage and promote exocytosis in chromaffin cells. J Neurochem 73:2397–2405Google Scholar
  138. Namkung Y, Sibley DR (2004) Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor. J Biol Chem 279:49533–49541Google Scholar
  139. Nickell JR, Siripurapu KB, Vartak A, Crooks PA, Dwoskin LP (2014) The vesicular monoamine transporter-2: an important pharmacological target for the discovery of novel therapeutics to treat methamphetamine abuse. Adv Pharmacol 69:71–106Google Scholar
  140. Niddam R, Arbilla S, Scatton B, Dennis T, Langer SZ (1985) Amphetamine induced release of endogenous dopamine in vitro is not reduced following pretreatment with reserpine. Naunyn Schmiedeberg’s Arch Pharmacol 329:123–127Google Scholar
  141. Nimitvilai S, McElvain MA, Brodie MS (2013) Reversal of dopamine D2 agonist-induced inhibition of ventral tegmental area neurons by Gq-linked neurotransmitters is dependent on protein kinase C, G protein-coupled receptor kinase, and dynamin. J Pharmacol Exp Ther 344:253–263Google Scholar
  142. Nomikos GG, Damsma G, Wenkstern D, Fibiger HC (1990) In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis. Synapse 6:106–112Google Scholar
  143. O’Brian CA, Liskamp RM, Solomon DH, Weinstein IB (1985) Inhibition of protein kinase C by tamoxifen. Cancer Res 45:2462–2465Google Scholar
  144. Ofori S, Bretton C, Hof P, Schorderet M (1986) Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro: I. Effects of dopamine precursors, reserpine, amphetamine, and L-DOPA decarboxylase and monoamine oxidase inhibitors. J Neurochem 47:1199–1206Google Scholar
  145. Pariser JJ, Partilla JS, Dersch CM, Ananthan S, Rothman RB (2008) Studies of the biogenic amine transporters. 12. Identification of novel partial inhibitors of amphetamine-induced dopamine release. J Pharmacol Exp Ther 326:286–295Google Scholar
  146. Parker EM, Cubeddu LX (1986) Effects of d-amphetamine and dopamine synthesis inhibitors on dopamine and acetylcholine neurotransmission in the striatum. I. Release in the absence of vesicular transmitter stores. J Pharmacol Exp Ther 237:179–192Google Scholar
  147. Partilla JS, Dempsey AG, Nagpal AS, Blough BE, Baumann MH, Rothman RB (2006) Interaction of amphetamines and related compounds at the vesicular monoamine transporter. J Pharmacol Exp Ther 319:237–246Google Scholar
  148. Patel J, Mooslehner KA, Chan PM, Emson PC, Stamford JA (2003) Presynaptic control of striatal dopamine neurotransmission in adult vesicular monoamine transporter 2 (VMAT2) mutant mice. J Neurochem 85:898–910Google Scholar
  149. Penmatsa A, Wang KH, Gouaux E (2015) X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat Struct Mol Biol 22:506–508Google Scholar
  150. Peter D, Jimenez J, Liu Y, Kim J, Edwards RH (1994) The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors. J Biol Chem 269:7231–7237Google Scholar
  151. Pierce RC, Kalivas PW (1997) Repeated cocaine modifies the mechanism by which amphetamine releases dopamine. J Neurosci 17:3254–3261Google Scholar
  152. Pierce RC, Quick EA, Reeder DC, Morgan ZR, Kalivas PW (1998) Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine. J Pharmacol Exp Ther 286:1171–1176Google Scholar
  153. Pifl C, Drobny H, Reither H, Hornykiewicz O, Singer EA (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol 47:368–373Google Scholar
  154. Pizzo AB, Karam CS, Zhang Y, Yano H, Freyberg RJ, Karam DS, Freyberg Z, Yamamoto A, McCabe BD, Javitch JA (2013) The membrane raft protein Flotillin-1 is essential in dopamine neurons for amphetamine-induced behavior in Drosophila. Mol Psychiatry 18:824–833Google Scholar
  155. Pizzo AB, Karam CS, Zhang Y, Ma CL, McCabe BD, Javitch JA (2014) Amphetamine-induced behavior requires CaMKII-dependent dopamine transporter phosphorylation. Mol Psychiatry 19:279–281Google Scholar
  156. Raiteri M, Bertollini A, del Carmine R, Levi G (1976) Release of biogenic amines from isolated nerve endings. Adv Exp Med Biol 69:319–335Google Scholar
  157. Ramamoorthy S, Shippenberg TS, Jayanthi LD (2011) Regulation of monoamine transporters: role of transporter phosphorylation. Pharmacol Ther 129:220–238Google Scholar
  158. Rastedt DE, Vaughan RA, Foster JD (2017) Palmitoylation mechanisms in dopamine transporter regulation. J Chem Neuroanat 83-84:3–9Google Scholar
  159. Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL (2015) Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter. Drug Alcohol Depend 147:1–19Google Scholar
  160. Richards TL, Zahniser NR (2009) Rapid substrate-induced down-regulation in function and surface localization of dopamine transporters: rat dorsal striatum versus nucleus accumbens. J Neurochem 108:1575–1584Google Scholar
  161. Rickhag M, Owens WA, Winkler MT, Strandfelt KN, Rathje M, Sorensen G, Andresen B, Madsen KL, Jorgensen TN, Wortwein G, Woldbye DP, Sitte H, Daws LC, Gether U (2013) Membrane-permeable C-terminal dopamine transporter peptides attenuate amphetamine-evoked dopamine release. J Biol Chem 288:27534–27544Google Scholar
  162. Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198Google Scholar
  163. Ross SB, Renyi AL (1966) Uptake of tritiated tyramine and (+) amphetamine by mouse heart slices. J Pharm Pharmacol 18:756–757Google Scholar
  164. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41Google Scholar
  165. Rothman RB, Dersch CM, Ananthan S, Partilla JS (2009) Studies of the biogenic amine transporters. 13. Identification of “agonist” and “antagonist” allosteric modulators of amphetamine-induced dopamine release. J Pharmacol Exp Ther 329:718–728Google Scholar
  166. Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE (2012) Studies of the biogenic amine transporters. 14. Identification of low-efficacy “partial” substrates for the biogenic amine transporters. J Pharmacol Exp Ther 341:251–262Google Scholar
  167. Rudnick G, Clark J (1993) From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters. Biochim Biophys Acta 1144:249–263Google Scholar
  168. Sabol KE, Seiden LS (1998) Reserpine attenuates D-amphetamine and MDMA-induced transmitter release in vivo: a consideration of dose, core temperature and dopamine synthesis. Brain Res 806:69–78Google Scholar
  169. Sambo DO, Lin M, Owens A, Lebowitz JJ, Richardson B, Jagnarine DA, Shetty M, Rodriquez M, Alonge T, Ali M, Katz J, Yan L, Febo M, Henry LK, Bruijnzeel AW, Daws L, Khoshbouei H (2017) The sigma-1 receptor modulates methamphetamine dysregulation of dopamine neurotransmission. Nat Commun 8:2228Google Scholar
  170. Schmitt KC, Reith ME (2010) Regulation of the dopamine transporter: aspects relevant to psychostimulant drugs of abuse. Ann N Y Acad Sci 1187:316–340Google Scholar
  171. Schmitt KC, Reith ME (2011) The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS One 6:e25790Google Scholar
  172. Schmitt KC, Zhen J, Kharkar P, Mishra M, Chen N, Dutta AK, Reith ME (2008) Interaction of cocaine-, benztropine-, and GBR12909-like compounds with wild-type and mutant human dopamine transporters: molecular features that differentially determine antagonist-binding properties. J Neurochem 107:928–940Google Scholar
  173. Schmitz Y, Lee CJ, Schmauss C, Gonon F, Sulzer D (2001) Amphetamine distorts stimulation-dependent dopamine overflow: effects on D2 autoreceptors, transporters, and synaptic vesicle stores. J Neurosci 21:5916–5924Google Scholar
  174. Schwartzberg L, Hermann R, Flinn I, Flora D, Hsi ED, Hamid O, Shi P, Lin BK, Myrand SP, Nguyen TS, Dreyling M (2014) Open-label, single-arm, phase II study of enzastaurin in patients with follicular lymphoma. Br J Haematol 166:91–97Google Scholar
  175. Seidel S, Singer EA, Just H, Farhan H, Scholze P, Kudlacek O, Holy M, Koppatz K, Krivanek P, Freissmuth M, Sitte HH (2005) Amphetamines take two to tango: an oligomer-based counter-transport model of neurotransmitter transport explores the amphetamine action. Mol Pharmacol 67:140–151Google Scholar
  176. Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB (2008) Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv 63:163–181Google Scholar
  177. Shi L, Quick M, Zhao Y, Weinstein H, Javitch JA (2008) The mechanism of a neurotransmitter:sodium symporter – inward release of Na+ and substrate is triggered by substrate in a second binding site. Mol Cell 30:667–677Google Scholar
  178. Siciliano CA, Calipari ES, Ferris MJ, Jones SR (2014) Biphasic mechanisms of amphetamine action at the dopamine terminal. J Neurosci 34:5575–5582Google Scholar
  179. Singh SK, Yamashita A, Gouaux E (2007) Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature 448:952–956Google Scholar
  180. Singh SK, Piscitelli CL, Yamashita A, Gouaux E (2008) A competitive inhibitor traps LeuT in an open-to-out conformation. Science 322:1655–1661Google Scholar
  181. Sitte HH, Freissmuth M (2010) The reverse operation of Na(+)/Cl(-)-coupled neurotransmitter transporters – why amphetamines take two to tango. J Neurochem 112:340–355Google Scholar
  182. Sitte HH, Freissmuth M (2015) Amphetamines, new psychoactive drugs and the monoamine transporter cycle. Trends Pharmacol Sci 36:41–50Google Scholar
  183. Sitte HH, Huck S, Reither H, Boehm S, Singer EA, Pifl C (1998) Carrier-mediated release, transport rates, and charge transfer induced by amphetamine, tyramine, and dopamine in mammalian cells transfected with the human dopamine transporter. J Neurochem 71:1289–1297Google Scholar
  184. Smith CB (1963) Enhancement by reserpine and alpha-methyl dopa of the effects of D-amphetamine upon the locomotor activity of mice. J Pharmacol Exp Ther 142:343–350Google Scholar
  185. Solis E Jr, Suyama JA, Lazenka MF, DeFelice LJ, Negus SS, Blough BE, Banks ML (2016) Dissociable effects of the prodrug phendimetrazine and its metabolite phenmetrazine at dopamine transporters. Sci Rep 6:31385Google Scholar
  186. Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (1997) Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants. J Neurosci 17:960–974Google Scholar
  187. Sorkina T, Doolen S, Galperin E, Zahniser NR, Sorkin A (2003) Oligomerization of dopamine transporters visualized in living cells by fluorescence resonance energy transfer microscopy. J Biol Chem 278:28274–28283Google Scholar
  188. Steinkellner T, Yang JW, Montgomery TR, Chen WQ, Winkler MT, Sucic S, Lubec G, Freissmuth M, Elgersma Y, Sitte HH, Kudlacek O (2012) Ca(2+)/calmodulin-dependent protein kinase IIalpha (alphaCaMKII) controls the activity of the dopamine transporter: implications for Angelman syndrome. J Biol Chem 287:29627–29635Google Scholar
  189. Stolerman IP, Garcha HS, Mirza NR (1995) Dissociations between the locomotor stimulant and depressant effects of nicotinic agonists in rats. Psychopharmacology 117:430–437Google Scholar
  190. Stolzenberg S, Quick M, Zhao C, Gotfryd K, Khelashvili G, Gether U, Loland CJ, Javitch JA, Noskov S, Weinstein H, Shi L (2015) Mechanism of the association between Na+ binding and conformations at the intracellular gate in neurotransmitter: sodium symporters. J Biol Chem 290:13992–14003Google Scholar
  191. Su HD, Mazzei GJ, Vogler WR, Kuo JF (1985) Effect of tamoxifen, a nonsteroidal antiestrogen, on phospholipid/calcium-dependent protein kinase and phosphorylation of its endogenous substrate proteins from the rat brain and ovary. Biochem Pharmacol 34:3649–3653Google Scholar
  192. Sulzer D (2011) How addictive drugs disrupt presynaptic dopamine neurotransmission. Neuron 69:628–649Google Scholar
  193. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 15:4102–4108Google Scholar
  194. Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75:406–433Google Scholar
  195. Teng L, Crooks PA, Dwoskin LP (1998) Lobeline displaces [3H]dihydrotetrabenazine binding and releases [3H]dopamine from rat striatal synaptic vesicles: comparison with d-amphetamine. J Neurochem 71:258–265Google Scholar
  196. Thoenen H, Hurlimann A, Haefely W (1968) Mechanism of amphetamine accumulation in the isolated perfused heart of the rat. J Pharm Pharmacol 20:1–11Google Scholar
  197. Vaughan RA, Huff RA, Uhl GR, Kuhar MJ (1997) Protein kinase C-mediated phosphorylation and functional regulation of dopamine transporters in striatal synaptosomes. J Biol Chem 272:15541–15546Google Scholar
  198. Vezina P (2004) Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27:827–839Google Scholar
  199. Vezina P, Lorrain DS, Arnold GM, Austin JD, Suto N (2002) Sensitization of midbrain dopamine neuron reactivity promotes the pursuit of amphetamine. J Neurosci 22:4654–4662Google Scholar
  200. Wall SC, Gu H, Rudnick G (1995) Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 47:544–550Google Scholar
  201. Wallis GG, Mc HJ, Scott OC (1949) Acute psychosis caused by dextro-amphetamine. Br Med J 2:1394Google Scholar
  202. Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, Miller GW, Wightman RM, Caron MG (1997) Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron 19:1285–1296Google Scholar
  203. Wang KH, Penmatsa A, Gouaux E (2015) Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature 521:322–327Google Scholar
  204. Wang Q, Bubula N, Brown J, Wang Y, Kondev V, Vezina P (2016) PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux. Neurosci Lett 622:78–82Google Scholar
  205. Weissman A, Koe BK, Tenen SS (1966) Antiamphetamine effects following inhibition of tyrosine hydroxylase. J Pharmacol Exp Ther 151:339–352Google Scholar
  206. Wieczorek WJ, Kruk ZL (1994) Differential action of (+)-amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens. Br J Pharmacol 111:829–836Google Scholar
  207. Wise RA, Bozarth MA (1985) Brain mechanisms of drug reward and euphoria. Psychiatr Med 3:445–460Google Scholar
  208. Xu C, Coffey LL, Reith ME (1995) Translocation of dopamine and binding of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane (WIN 35,428) measured under identical conditions in rat striatal synaptosomal preparations. Inhibition by various blockers. Biochem Pharmacol 49:339–350Google Scholar
  209. Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E (2005) Crystal structure of a bacterial homologue of Na+/Cl−-dependent neurotransmitter transporters. Nature 437:215–223Google Scholar
  210. Zaczek R, Culp S, De Souza EB (1991) Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport. J Pharmacol Exp Ther 257:830–835Google Scholar
  211. Zahniser NR, Sorkin A (2009) Trafficking of dopamine transporters in psychostimulant actions. Semin Cell Dev Biol 20:411–417Google Scholar
  212. Zarate CA, Manji HK (2009) Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 23:569–582Google Scholar
  213. Zestos AG, Mikelman SR, Kennedy RT, Gnegy ME (2016) PKCbeta inhibitors attenuate amphetamine-stimulated dopamine efflux. ACS Chem Neurosci 7:757–766Google Scholar
  214. Zestos AG, Carpenter C, Kim Y, Low MJ, Kennedy RT, Gnegy ME (2019) Ruboxistaurin reduces cocaine-stimulated increases in extracellular dopamine by modifying dopamine-autoreceptor activity. ACS Chem Neurosci 10:1960–1969Google Scholar
  215. Zetterstrom T, Sharp T, Collin AK, Ungerstedt U (1988) In vivo measurement of extracellular dopamine and DOPAC in rat striatum after various dopamine-releasing drugs; implications for the origin of extracellular DOPAC. Eur J Pharmacol 148:327–334Google Scholar
  216. Zhou Z, Zhen J, Karpowich NK, Goetz RM, Law CJ, Reith ME, Wang DN (2007) LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake. Science 317:1390–1393Google Scholar
  217. Zhu HJ, Appel DI, Grundemann D, Markowitz JS (2010) Interaction of organic cation transporter 3 (SLC22A3) and amphetamine. J Neurochem 114:142–149Google Scholar
  218. Zimanyi I, Lajtha A, Reith ME (1989) Comparison of characteristics of dopamine uptake and mazindol binding in mouse striatum. Naunyn Schmiedeberg’s Arch Pharmacol 340:626–632Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PsychiatryNew York University School of MedicineNew YorkUSA
  2. 2.Department of PharmacologyUniversity of Michigan School of MedicineAnn ArborUSA

Personalised recommendations