Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake

Journal of Neuroscience

Volumn 32, Issue 49, 2012, Pages 17582-17596

  Schindler, Abigail G ^a   Messinger, Daniel I ^a   Smith, Jeffrey S ^a   Shankar, Haripriya ^a   Gustin, Richard M ^a   Schattauer, Selena S ^a   Lemos, Julia C ^a   Chavkin, Nicholas W ^a   Hagan, Catherine E ^a   Neumaier, John F ^a   Chavkin, Charles ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COCAINE; DOPAMINE; DYNORPHIN; KAPPA OPIATE RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE P38; SEROTONIN; SEROTONIN TRANSPORTER;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AVERSION; CONTROLLED STUDY; CORPUS STRIATUM; DORSAL RAPHE NUCLEUS; FORCED SWIMMING TEST; GENOTYPE; IMMUNOHISTOCHEMISTRY; KNOCKOUT MOUSE; MALE; MOUSE; NONHUMAN; PLACE PREFERENCE; POLYMERASE CHAIN REACTION; POTENTIOMETRY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REWARD; STRESS; TRANSGENIC MOUSE; WESTERN BLOTTING;

ANIMALS; AVOIDANCE LEARNING; BRAIN; COCAINE; CORPUS STRIATUM; DOPAMINE; DYNORPHINS; G-PROTEIN-COUPLED RECEPTOR KINASE 3; MALE; MEMBRANE TRANSPORT PROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; MICROINJECTIONS; NALTREXONE; NARCOTIC ANTAGONISTS; NICOTINE; NUCLEUS ACCUMBENS; P38 MITOGEN-ACTIVATED PROTEIN KINASES; RAPHE NUCLEI; RECEPTORS, OPIOID, KAPPA; REWARD; SEROTONIN; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SIGNAL TRANSDUCTION; STRESS, PSYCHOLOGICAL; SUBSTANCE WITHDRAWAL SYNDROME; SYNAPTOSOMES;

EID: 84870545189     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3220-12.2012     Document Type: Article

References (88)

1. Adell A, Casanovas JM, Artigas F (1997) Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas. Neuropharmacology 36:735-741. CrossRef Medline
2. Awtry TL, Werling LL (2003) Acute and chronic effects of nicotine on serotonin uptake in prefrontal cortex and hippocampus of rats. Synapse 50: 206-211. CrossRef Medline
3. Baganz N, Horton R, Martin K, Holmes A, Daws LC (2010) Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun. J Neurosci 30:15185-15195. CrossRef Medline
4. Berton O, Durand M, Aguerre S, Mormède P, Chaouloff F (1999) Behavioral, neuroendocrine and serotonergic consequences of single social defeat and repeated fluoxetine pretreatment in the Lewis rat strain. Neuroscience 92:327-341. CrossRef Medline
5. Bruchas MR, Macey TA, Lowe JD, Chavkin C (2006) Kappa opioid receptor activation of p38MAPKis GRK3- and arrestin-dependent in neurons and astrocytes. J Biol Chem 281:18081-18089. CrossRef Medline
6. Bruchas MR, Land BB, Aita M, Xu M, Barot SK, Li S, Chavkin C (2007a) Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria. J Neurosci 27:11614-11623. CrossRef Medline
7. Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C (2007b) Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase. J Biol Chem 282:29803-29811. CrossRef Medline
8. Bruchas MR, Land BB, Chavkin C (2010) The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Res 1314:44-55. CrossRef Medline
9. Bruchas MR, Schindler AG, Shankar H, Messinger DI, Miyatake M, Land BB, Lemos JC, Hagan CE, Neumaier JF, Quintana A, Palmiter RD, Chavkin C (2011) Selective p38alpha MAPK deletion in serotonergic neurons produces stress resilience in models of depression and addiction. Neuron 71:498-511. CrossRef Medline
10. Burnette WB, Bailey MD, Kukoyi S, Blakely RD, Trowbridge CG, Justice JB Jr (1996) Human norepinephrine transporter kinetics using rotating disk electrode voltammetry. Anal Chem 68:2932-2938. CrossRef Medline
11. Carlezon WA Jr, Béguin C, DiNieri JA, Baumann MH, Richards MR, Todtenkopf MS, Rothman RB, Ma Z, Lee DY, Cohen BM (2006) Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharmacol Exp Ther 316:440-447. Medline
12. Carlezon WA Jr, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ (1998) Regulation of cocaine reward by CREB. Science 282:2272-2275. CrossRef Medline
13. Chau DT, Rada PV, Kim K, Kosloff RA, Hoebel BG (2011) Fluoxetine alle-viates behavioral depression while decreasing acetylcholine release in the nucleus accumbens shell. Neuropsychopharmacology 36:1729-1737. CrossRef Medline
14. Connor TJ, Kelliher P, Harkin A, Kelly JP, Leonard BE (1999a) Reboxetine attenuates forced swim test-induced behavioural and neurochemical alterations in the rat. Eur J Pharmacol 379:125-133. CrossRef Medline
15. Connor TJ, Song C, Leonard BE, Anisman H, Merali Z (1999b) Stressorinduced alterations in serotonergic activity in an animal model of depression. Neuroreport 10:523-528. CrossRef Medline
16. Coppen AJ, Doogan DP (1988) Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry 49 [Suppl]:4-11. Medline
17. Daws LC (2009) Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy. Pharmacol Ther 121:89-99. CrossRef Medline
18. De La Garza R 2nd, Mahoney JJ 3rd (2004) A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal models of anxiety and depression. Brain Res 1021:209-218. CrossRef Medline
19. Earles C, Schenk JO (1998) Rotating disk electrode voltammetric measurements of dopamine transporter activity: an analytical evaluation. Anal Biochem 264:191-198. CrossRef Medline
20. El Yacoubi M, Bouali S, Popa D, Naudon L, Leroux-Nicollet I, Hamon M, Costentin J, Adrien J, Vaugeois JM (2003) Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci U S A 100:6227-6232. CrossRef Medline
21. Fletcher PJ, Korth KM, Chambers JW (1999) Selective destruction of brain serotonin neurons by 5,7-dihydroxytryptamine increases responding for a conditioned reward. Psychopharmacology (Berl) 147:291-299. CrossRef Medline
22. Fletcher PJ, Rizos Z, Noble K, Soko AD, Silenieks LB, Lê AD, Higgins GA (2012) Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement. Neuropharmacology 62:2288-2298. CrossRef Medline
23. Haenisch B, Bönisch H (2011) Depression and antidepressants: insights from knockout of dopamine, serotonin or noradrenaline re-uptake transporters. Pharmacol Ther 129:352-368. CrossRef Medline
24. Hagan CE, Neumaier JF, Schenk JO (2010) Rotating disk electrode voltammetric measurements of serotonin transporter kinetics in synaptosomes. J Neurosci Methods 193:29-38. CrossRef Medline
25. Hagan CE, Schenk JO, Neumaier JF (2011) The contribution of low-affinity transport mechanisms to serotonin clearance in synaptosomes. Synapse 65:1015-1023. CrossRef Medline
26. Hara Y, Yakovleva T, Bakalkin G, Pickel VM (2006) Dopamine D1 receptors have subcellular distributions conducive to interactions with prodynorphin in the rat nucleus accumbens shell. Synapse 60:1-19. CrossRef Medline
27. Harris GC, Altomare K, Aston-Jones G (2001) Preference for a cocaineassociated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats. Psychopharmacology (Berl) 156:14-22. CrossRef Medline
28. Heinz A, Ragan P, Jones DW, Hommer D, Williams W, Knable MB, Gorey JG, Doty L, Geyer C, Lee KS, Coppola R, Weinberger DR, Linnoila M (1998) Reduced central serotonin transporters in alcoholism. Am J Psychiatry 155:1544-1549. Medline
29. Horan P, Taylor J, Yamamura HI, Porreca F (1992) Extremely long-lasting antagonistic actions of nor-binaltorphimine (nor-BNI) in the mouse tailflick test. J Pharmacol Exp Ther 260:1237-1243. Medline
30. Hough LB, Nalwalk JW, Chen Y, Schuller A, Zhu Y, Zhang J, Menge WM, Leurs R, Timmerman H, Pintar JE (2000) Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice. Brain Res 880:102-108. CrossRef Medline
31. Jackson KJ, Carroll FI, Negus SS, Damaj MI (2010) Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse. Psychopharmacology (Berl) 210: 285-294. CrossRef Medline
32. Kenny PJ, Markou A (2001) Neurobiology of the nicotine withdrawal syndrome. Pharmacol Biochem Behav 70:531-549. CrossRef Medline
33. Kirby LG, Lucki I (1997) Interaction between the forced swimming test and fluoxetine treatment on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat. J Pharmacol Exp Ther 282:967-976. Medline
34. Kirby LG, Allen AR, Lucki I (1995) Regional differences in the effects of forced swimming on extracellular levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 682:189-196. CrossRef Medline
35. Knoll AT, Carlezon WA Jr (2010) Dynorphin, stress, and depression. Brain Res 1314:56-73. CrossRef Medline
36. Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11-34. CrossRef Medline
37. Koob GF, Le Moal M (2005) Plasticity of reward neurocircuitry and the 'dark side' of drug addiction. Nat Neurosci 8:1442-1444. CrossRef Medline
38. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894-902. CrossRef Medline
39. Kuhar MJ (1992) Molecular pharmacology of cocaine: a dopamine hypothesis and its implications. Ciba Found Symp 166:81-89; discussion 89-95. Medline
40. Laasonen-Balk T, Kuikka J, Viinamäki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (1999) Striatal dopamine transporter density in major depression. Psychopharmacology (Berl) 144:282-285. CrossRef Medline
41. Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C (2008) The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci 28:407-414. CrossRef Medline
42. Land BB, Bruchas MR, Schattauer S, Giardino WJ, Aita M, Messinger D, Hnasko TS, Palmiter RD, Chavkin C (2009) Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking. Proc Natl Acad Sci U S A 106:19168-19173. CrossRef Medline
43. Lê AD, Poulos CX, Harding S, Watchus J, Juzytsch W, Shaham Y (1999) Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress. Neuropsychopharmacology 21:435-444. CrossRef Medline
44. Lee JH, Kim HJ, Kim JG, Ryu V, Kim BT, Kang DW, Jahng JW (2007) Depressive behaviors and decreased expression of serotonin reuptake transporter in rats that experienced neonatal maternal separation. Neurosci Res 58:32-39. CrossRef Medline
45. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL (1996) Association of anxietyrelated traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527-1531. CrossRef Medline
46. Lira A, Zhou M, Castanon N, Ansorge MS, Gordon JA, Francis JH, Bradley-Moore M, Lira J, Underwood MD, Arango V, Kung HF, Hofer MA, Hen R, Gingrich JA (2003) Altered depression-related behaviors and functional changes in the dorsal raphe nucleus of serotonin transporterdeficient mice. Biol Psychiatry 54:960-971. CrossRef Medline
47. Loh EA, Roberts DC (1990) Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology (Berl) 101:262-266. CrossRef Medline
48. Ma J, Ye N, Lange N, Cohen BM (2003) Dynorphinergic GABA neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus. Neuroscience 121:991-998. CrossRef Medline
49. Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L, Sanacora G, Owens MJ, Nemeroff CB, Rajeevan N, Baldwin RM, Seibyl JP, Innis RB, Charney DS (1998) Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 44:1090-1098. CrossRef Medline
50. Martin C, Duclos M, Mormède P, Manier G, Chaouloff F (2000) Hippocampal and striatal [(3)H]5-HT reuptake under acute stressors in two rat strains differing for their emotivity. Neurosci Lett 288:246-248. CrossRef Medline
51. Maskos U, Molles BE, Pons S, Besson M, Guiard BP, Guilloux JP, Evrard A, Cazala P, Cormier A, Mameli-Engvall M, Dufour N, Cloëz-Tayarani I, Bemelmans AP, Mallet J, Gardier AM, David V, Faure P, Granon S, Changeux JP (2005) Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors. Nature 436:103-107. CrossRef Medline
52. McLaughlin JP, Marton-Popovici M, Chavkin C (2003a) Kappa opioid receptor antagonism and prodynorphin gene disruption block stressinduced behavioral responses. J Neurosci 23:5674-5683. Medline
53. McLaughlin JP, Xu M, Mackie K, Chavkin C (2003b) Phosphorylation of a carboxyl-terminal serine within the kappa-opioid receptor produces desensitization and internalization. J Biol Chem 278:34631-34640. CrossRef Medline
54. McLaughlin JP, Myers LC, Zarek PE, Caron MG, Lefkowitz RJ, Czyzyk TA, Pintar JE, Chavkin C (2004) Prolonged kappa opioid receptor phosphorylation mediated by G-protein receptor kinase underlies sustained analgesic tolerance. J Biol Chem 279:1810-1818. CrossRef Medline
55. Merali Z, Lacosta S, Anisman H (1997) Effects of interleukin-1beta and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study. Brain Res 761:225-235. CrossRef Medline
56. Nishida K, Yamaguchi O, Hirotani S, Hikoso S, Higuchi Y, Watanabe T, Takeda T, Osuka S, Morita T, Kondoh G, Uno Y, Kashiwase K, Taniike M, Nakai A, Matsumura Y, Miyazaki J, Sudo T, Hongo K, Kusakari Y, Kurihara S, et al. (2004) p38alpha mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure overload. Mol Cell Biol 24:10611-10620. CrossRef Medline
57. Parsons LH, Koob GF, Weiss F (1995) Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine. J Pharmacol Exp Ther 274:1182-1191. Medline
58. Peppel K, Boekhoff I, McDonald P, Breer H, Caron MG, Lefkowitz RJ (1997) G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. J Biol Chem 272:25425-25428. CrossRef Medline
59. Pfeiffer A, Brantl V, Herz A, Emrich HM (1986) Psychotomimeis mediated by kappa opioid receptors. Science 233:774-776. CrossRef Medline
60. Pliakas AM, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon WA Jr (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response elementbinding protein expression in nucleus accumbens. J Neurosci 21:7397-7403. Medline
61. Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730-732. CrossRef Medline
62. Racca S, Spaccamiglio A, Esculapio P, Abbadessa G, Cangemi L, DiCarlo F, Portaleone P (2005) Effects of swim stress and alpha-MSH acute pretreatment on brain 5-HT transporter and corticosterone receptor. Pharmacol Biochem Behav 81:894-900. CrossRef Medline
63. Ramamoorthy S, Shippenberg TS, Jayanthi LD (2011) Regulation of monoamine transporters: role of transporter phosphorylation. Pharmacol Ther 129:220-238. CrossRef Medline
64. Samuvel DJ, Jayanthi LD, Bhat NR, Ramamoorthy S (2005) A role for p38 mitogen-activated protein kinase in the regulation of the serotonin transporter: evidence for distinct cellular mechanisms involved in transporter surface expression. J Neurosci 25:29-41. CrossRef Medline
65. Schenk JO, Wright C, Bjorklund N (2005) Unraveling neuronal dopamine transporter mechanisms with rotating disk electrode voltammetry. J Neurosci Methods 143:41-47. CrossRef Medline
66. Schindler AG, Li S, Chavkin C (2010) Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptormediated mechanism without affecting associative learning or memory retrieval mechanisms. Neuropsychopharmacology 35:1932-1942. CrossRef Medline
67. Scott MM, Krueger KC, Deneris ES (2005) A differentially autoregulated Pet-1 enhancer region is a critical target of the transcriptional cascade that governs serotonin neuron development. J Neurosci 25:2628-2636. CrossRef Medline
68. Shirayama Y, Ishida H, Iwata M, Hazama GI, Kawahara R, Duman RS (2004) Stress increases dynorphin immunoreactivity in limbic brain regions and dynorphin antagonism produces antidepressant-like effects. J Neurochem 90:1258-1268. CrossRef Medline
69. Sirven A, Ravet E, Charneau P, Zennou V, Coulombel L, Guétard D, Pflumio F, Dubart-Kupperschmitt A (2001) Enhanced transgene expression in cord blood CD34(α)-derived hematopoietic cells, including developing T cells and NOD/SCID mouse repopulating cells, following transduction with modified trip lentiviral vectors. Mol Ther 3:438-448. CrossRef Medline
70. Smith JE, Shultz K, Co C, Goeders NE, Dworkin SI (1987) Effects of 5,7- dihydroxytryptamine lesions of the nucleus accumbens on rat intravenous morphine self-administration. Pharmacol Biochem Behav 26: 607-612. CrossRef Medline
71. Smith JS, Schindler AG, Martinelli E, Gustin RM, Bruchas MR, Chavkin C (2012) Stress-induced activation of the dynorphin/kappa-opioid receptor system in the amygdala potentiates nicotine conditioned place preference. J Neurosci 32:1488-1495. CrossRef Medline
72. Sora I, Hall FS, Andrews AM, Itokawa M, Li XF, Wei HB, Wichems C, Lesch KP, Murphy DL, Uhl GR (2001) Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Natl Acad Sci U S A 98:5300-5305. CrossRef Medline
73. Sperling RE, Gomes SM, Sypek EI, Carey AN, McLaughlin JP (2010) Endogenous kappa-opioid mediation of stress-induced potentiation of ethanol-conditioned place preference and self-administration. Psychopharmacology (Berl) 210: 199-209. CrossRef Medline
74. Steiner JA, Carneiro AM, Blakely RD (2008) Going with the flow: trafficking-dependent and -independent regulation of serotonin transport. Traffic 9:1393-1402. CrossRef Medline
75. Svingos AL, Colago EE, Pickel VM (1999) Cellular sites for dynorphin activation of kappa-opioid receptors in the rat nucleus accumbens shell. J Neurosci 19:1804-1813. Medline
76. Tallquist MD, Soriano P (2000) Epiblast-restricted Cre expression in MORE mice: a tool to distinguish embryonic vs. extra-embryonic gene function. Genesis 26:113-115. CrossRef Medline
77. Tao R, Auerbach SB (2002) Opioid receptor subtypes differentially modulate serotonin efflux in the rat central nervous system. J Pharmacol Exp Ther 303:549-556. CrossRef Medline
78. Torres GE, Gainetdinov RR, Caron MG (2003) Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci 4:13-25. CrossRef Medline
79. Turchan J, Przewlocka B, Lason W, Przewlocki R (1998) Effects of repeated psychostimulant administration on the prodynorphin system activity and kappa opioid receptor density in the rat brain. Neuroscience 85:1051-1059. CrossRef Medline
80. Walsh SL, Cunningham KA (1997) Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine. Psychopharmacology (Berl) 130:41-58. CrossRef Medline
81. Watanabe Y, Sakai RR, McEwen BS, Mendelson S (1993) Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin. Brain Res 615:87-94. CrossRef Medline
82. Wellman CL, Izquierdo A, Garrett JE, Martin KP, Carroll J, Millstein R, Lesch KP, Murphy DL, Holmes A (2007) Impaired stress-coping and fear extinction and abnormal corticolimbic morphology in serotonin transporter knock-out mice. J Neurosci 27:684-691. CrossRef Medline
83. Xu M, Petraschka M, McLaughlin JP, Westenbroek RE, Caron MG, Lefkowitz RJ, Czyzyk TA, Pintar JE, Terman GW, Chavkin C (2004) Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. J Neurosci 24:4576-4584. CrossRef Medline
84. Zhang Y, Butelman ER, Schlussman SD, Ho A, Kreek MJ (2005) Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Psychopharmacology 179: 551-558. CrossRef Medline
85. Zhu CB, Hewlett WA, Feoktistov I, Biaggioni I, Blakely RD (2004) Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation. Mol Pharmacol 65:1462-1474. CrossRef Medline
86. Zhu CB, Carneiro AM, Dostmann WR, Hewlett WA, Blakely RD (2005) p38 MAPK activation elevates serotonin transport activity via a traffickingindependent, protein phosphatase 2A-dependent process. J Biol Chem 280:15649-15658. CrossRef Medline
87. Zhu CB, Lindler KM, Owens AW, Daws LC, Blakely RD, Hewlett WA (2010) Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters. Neuropsychopharmacology 35:2510-2520. CrossRef Medline
88. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D (1998) Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J Virol 72:9873-9880. Medline