Akt/GSK3 signaling in the action of psychotropic drugs

Annual Review of Pharmacology and Toxicology

Volumn 49, Issue , 2009, Pages 327-347

  Beaulieu, Jean Martin ^a   Gainetdinov, Raul R ^b,c   Caron, Marc G ^b  

^a UNIVERSITÉ LAVAL   (Canada)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

Dopamine; Monoamine; Psychiatric disorders; Serotonin; Signaling

Indexed keywords

1 ISOPROPYL 6 METHYLERGOLINE 8 CARBOXYLIC ACID 2 HYDROXY 1 METHYLPROPYL ESTER; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; ANTIDEPRESSANT AGENT; BETA ARRESTIN 2; BETA CATENIN; CLOZAPINE; DOPAMINE; DOPAMINE 2 RECEPTOR; G PROTEIN COUPLED RECEPTOR; GLUTAMATE RECEPTOR; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; HALOPERIDOL; LAMOTRIGINE; LITHIUM; MOOD STABILIZER; NEUROLEPTIC AGENT; OLANZAPINE; PROTEIN KINASE B; PSYCHOTROPIC AGENT; QUETIAPINE; RISPERIDONE; SEROTONIN; SEROTONIN UPTAKE INHIBITOR; VALPROIC ACID; ZIPRASIDONE; LITHIUM DERIVATIVE;

BEHAVIOR; BIPOLAR DISORDER; CIRCADIAN RHYTHM; DRUG EFFECT; DRUG MECHANISM; LOCOMOTION; MAJOR DEPRESSION; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SCHIZOPHRENIA; SIGNAL TRANSDUCTION; ANIMAL; HUMAN; MENTAL DISEASE; METABOLISM; NOMENCLATURE; PATHOPHYSIOLOGY;

MUS;

ANIMALS; ANTIPSYCHOTIC AGENTS; GLYCOGEN SYNTHASE KINASE 3; HUMANS; LITHIUM COMPOUNDS; MENTAL DISORDERS; PROTO-ONCOGENE PROTEINS C-AKT; PSYCHOTROPIC DRUGS; SIGNAL TRANSDUCTION; TERMINOLOGY AS TOPIC;

EID: 62149119762     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev.pharmtox.011008.145634     Document Type: Review

References (142)

1. Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML. 2001. Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu. Rev. Pharmacol. Toxicol. 41:237-60
2. Glowinski J, Axelrod J. 1964. Inhibition of uptake of tritiated-noradrenaline in the intact rat brain by imipramine and structurally related compounds. Nature 204:1318-19
3. Creese I, Burt DR, Snyder SH. 1976. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481-83
4. Carlsson A, Fuxe K, Ungerstedt U. 1968. The effect of imipramine on central 5-hydroxytryptamine neurons. J. Pharm. Pharmacol. 20:150-51
5. Seeman P, Weinshenker D, Quirion R, Srivastava LK, Bhardwaj SK, et al. 2005. Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proc. Natl. Acad. Sci. USA 102:3513-18
6. Meltzer HY. 1991. The mechanism of action of novel antipsychotic drugs. Schizophr. Bull. 17:263-87
7. Roth BL, Sheffler DJ, Kroeze WK. 2004. Magic shotguns versus magic bullets: selectively nonselective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov. 3:353-59
8. Beaulieu JM, Gainetdinov RR, Caron MG. 2007. The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol. Sci. 28:166-72
9. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. 2007. Beta-arrestins and cell signaling. Annu. Rev. Physiol. 69:483-510
10. Galandrin S, Oligny-Longpre G, Bouvier M. 2007. The evasive nature of drug efficacy: implications for drug discovery. Trends Pharmacol. Sci. 28:423-30
11. Angers S, Salahpour A, Bouvier M. 2002. Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu. Rev. Pharmacol. Toxicol. 42:409-35
12. González-Maeso J, Ang RL, Yuen T, Chan P,Weisstaub NV, et al. 2008. Identification of a serotonin/ glutamate receptor complex implicated in psychosis. Nature 452:93-97
13. Lee SP, So CH, Rashid AJ, Varghese G, Cheng R, et al. 2004. Dopamine D1 and D2 receptor co-activation generates a novel phospholipase C-mediated calcium signal. J. Biol. Chem. 279:35671-78
14. Greengard P. 2001. The neurobiology of slow synaptic transmission. Science 294:1024-30
15. Andjelkovic M, Alessi DR, Meier R, Fernandez A, Lamb NJ, et al. 1997. Role of translocation in the activation and function of protein kinase B. J. Biol. Chem. 272:31515-24
16. Alessi DR, Cohen P. 1998. Mechanism of activation and function of protein kinase B. Curr. Opin. Genet. Dev. 8:55-62
17. Scheid MP,Woodgett JR. 2001. PKB/AKT: functional insights from genetic models. Nat. Rev.Mol. Cell Biol. 2:760-68
18. Jacinto E, Facchinetti V, Liu D, Soto N,Wei S, et al. 2006. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127:125-37
19. Embi N, Rylatt DB, Cohen P. 1980. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 107:519-27
20. Frame S, Cohen P. 2001. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 359:1-16
21. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785-89
22. Chen MJ, Russo-Neustadt AA. 2005. Exercise activates the phosphatidylinositol 3-kinase pathway. Brain Res. Mol. Brain Res. 135:181-93
23. Beaulieu JM, Sotnikova TD, Yao WD, Kockeritz L, Woodgett JR, et al. 2004. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc. Natl. Acad. Sci. USA 101:5099-104
24. Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG. 2006. Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. J. Biol. Chem. 281:32072-80
25. Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Carson MG. 2005. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122:261-73
26. Chen PC, Lao CL, Chen JC. 2007. Dual alteration of limbic dopamine D1 receptor-mediated signalling and the Akt/GSK3 pathway in dopamine D3 receptor mutants during the development of methamphetamine sensitization. J. Neurochem. 100:225-41
27. Bychkov E, Ahmed MR, Dalby KN, Gurevich EV. 2007. Dopamine depletion and subsequent treatment with L-DOPA, but not the long-lived dopamine agonist pergolide, enhances activity of the Akt pathway in the rat striatum. J. Neurochem. 102:699-711
28. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. 2004. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat. Genet. 36:131-37
29. Roh MS, Seo MS, Kim Y, Kim SH, Jeon WJ, et al. 2007. Haloperidol and clozapine differentially regulate signals upstream of glycogen synthase kinase 3 in the rat frontal cortex. Exp. Mol. Med. 39:353-60
30. Beaulieu JM, Tirotta E, Sotnikova TD, Masri B, Salahpour A, et al. 2007. Regulation of Akt signaling by D2 and D3 dopamine receptors in vivo. J. Neurosci. 27:881-85
31. Kebabian JW, Calne DB. 1979. Multiple receptors for dopamine. Nature 277:93-96
32. Kebabian JW, Greengard P. 1971. Dopamine-sensitive adenyl cyclase: possible role in synaptic transmission. Science 174:1346-49
33. Enjalbert A, Bockaert J. 1983. Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol. Pharmacol. 23:576-84
34. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. 1998. Dopamine receptors: from structure to function. Physiol. Rev. 78:189-225
35. Arriza JL, Dawson TM, Simerly RB, Martin LJ, Caron MG, et al. 1992. The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain. J. Neurosci. 12:4045-55
36. Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, et al. 1991. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. J. Biol. Chem. 266:14939-46
37. Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG.2004. Desensitization of Gprotein-coupled receptors and neuronal functions. Annu. Rev. Neurosci. 27:107-44
38. Shenoy SK, Lefkowitz RJ. 2003. Multifaceted roles of beta-arrestins in the regulation of sevenmembrane-spanning receptor trafficking and signalling. Biochem. J. 375:503-15
39. Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ. 1990. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248:1547-50
40. Ferguson SS, Downey WE 3rd, Colapietro AM, Barak LS, Ménard L, Carson MG. 1996. Role of betaarrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 271:363-66
41. Laporte SA, Miller WE, Kim KM, Caron MG. 2002. beta-Arrestin/AP-2 interaction in G proteincoupled receptor internalization: identification of a beta-arrestin binging site in beta 2-adaptin. J. Biol. Chem. 277:9247-54
42. Lefkowitz RJ, Shenoy SK. 2005. Transduction of receptor signals by beta-arrestins. Science 308:512-17
43. Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, et al. 1999. Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283:655-61
44. Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, et al. 2001. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc. Natl. Acad. Sci. USA 98:2449-54
45. Andjelkovic M, Jakubowicz T, Cron P, Ming XF, Han JW, et al. 1996. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc. Natl. Acad. Sci. USA 93:5699-704
46. Bohn LM,Gainetdinov RR, Sotnikova TD, Medvedev IO, Lefkowitz RJ, et al. 2003. Enhanced rewarding properties of morphine, but not cocaine, in beta(arrestin)-2 knock-out mice. J. Neurosci. 23:10265-73
47. Gould TD, Einat H, Bhat R, Manji HK. 2004. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int. J. Neuropsychopharmacol. 7:387-90
48. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, et al. 2000. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 406:86-90
49. Prickaerts J, Moechars D, Cryns K, Lenaerts I, van Craenendonck H, et al. 2006. Transgenic mice overexpressing glycogen synthase kinase 3β: a putative model of hyperactivity and mania. J. Neurosci. 26:9022-29
50. Powell SB, Geyer MA. 2007. Overview of animal models of schizophrenia. Curr. Protoc. Neurosci. Chapter 9:Unit 9.24
51. Carlsson A. 1987. Perspectives on the discovery of central monoaminergic neurotransmission. Annu. Rev. Neurosci. 10:19-40
52. Li X, Zhu W, Roh MS, Friedman AB, Rosborough K, et al. 2004. In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology 29:1426-31
53. Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA. 2007. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int. J. Neuropsychopharmacol. 10:7-19
54. Beaulieu JM. 2007. Not only lithium: regulation of glycogen synthase kinase-3 by antipsychotics and serotonergic drugs. Int. J. Neuropsychopharmacol. 10:3-6
55. Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, et al. 2008. Role of GSK3beta in behavioral abnormalities induced by serotonin deficiency. Proc. Natl. Acad. Sci. USA 105:1333-38
56. Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG. 2004. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 305:217
57. Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, et al. 2003. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299:76
58. Zhang X, Beaulieu JM, Gainetdinov RR, Caron MG. 2006. Functional polymorphisms of the brain serotonin synthesizing enzyme tryptophan hydroxylase-2. Cell Mol. Life Sci. 63:6-11
59. O'Brien WT, Harper AD, Jove F, Woodgett JR, Maretto S, et al. 2004. Glycogen synthase kinase-3β haploinsufficiency mimics the behavioral and molecular effects of lithium. J. Neurosci. 24:6791-98
60. Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, et al. 2008. Reply to Belmaker et al: GSK3β haploinsufficiency results in lithium-like effects in the forced swim test. Proc. Natl. Acad. Sci. USA 105:133-38
61. O'Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, et al. 2007. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology 192:357-71
62. Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, et al. 2005. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 45:11-16
63. Crowley JJ, Blendy JA, Lucki I. 2005. Strain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test. Psychopharmacology 183:257-64
64. Crowley JJ, Jones MD, O'Leary OF, Lucki I. 2004. Automated tests for measuring the effects of antidepressants in mice. Pharmacol. Biochem. Behav. 78:269-74
65. Lucki I, Dalvi A, Mayorga AJ. 2001. Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology 155:315-22
66. Weisstaub NV, Zhou M, Lira A, Lambe E, Gonzalez-Maeso J, et al. 2006. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313:536-40
67. Crawley J, Goodwin FK. 1980. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 13:167-70
68. Snyder SH. 1976. The dopamine hypothesis of schizophrenia: focus on the dopamine receptor. Am. J. Psychiatry 133:197-202
69. Kapur S, Remington G. 2001. Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia. Annu. Rev. Med. 52:503-17
70. Kang UG, Seo MS, Roh MS, Kim Y, Yoon SC, Kim YS. 2004. The effects of clozapine on the GSK-3-mediated signaling pathway. FEBS Lett. 560:115-19
71. Alimohamad H, Rajakumar N, Seah YH, Rushlow W. 2005. Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum. Biol. Psychiatry 57:533-42
72. Sutton LP, Honardoust D, Mouyal J, Rajakumar N, Rushlow WJ. 2007. Activation of the canonical Wnt pathway by the antipsychotics haloperidol and clozapine involves dishevelled-3. J. Neurochem. 102:153-69
73. Blanco C, Laje G, Olfson M, Marcus SC, Pincus HA. 2002. Trends in the treatment of bipolar disorder by outpatient psychiatrists. Am. J. Psychiatry 159:1005-10
74. Quiroz JA, Singh J, Gould TD, Denicoff KD, Zarate CA, et al. 2004. Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology. Mol. Psychiatry 9:756-76
75. Phiel CJ, Klein PS. 2001. Molecular targets of lithium action. Annu. Rev. Pharmacol. Toxicol. 41:789-813
76. De Montigny C, Grunberg F, Mayer A, Deschenes JP. 1981. Lithium induces rapid relief of depression in tricyclic antidepressant drug nonresponders. Br. J. Psychiatry 138:252-56
77. Klein PS, Melton DA. 1996. A molecular mechanism for the effect of lithium on development. Proc. Natl. Acad. Sci. USA 93:8455-59
78. Stambolic V, Ruel L, Woodgett JR. 1996. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr. Biol. 6:1664-68
79. Berridge MJ, Downes CP, Hanley MR. 1989. Neural and developmental actions of lithium: a unifying hypothesis. Cell 59:411-19
80. Birch NJ. 1974. Letter: Lithium and magnesium-dependent enzymes. Lancet 2:965-66
81. Ryves WJ, Harwood AJ. 2001. Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem. Biophys. Res. Commun. 280:720-25
82. Gurvich N, Klein PS. 2002. Lithium and valproic acid: parallels and contrasts in diverse signaling contexts. Pharmacol. Ther. 96:45-66
83. Gould TD, Chen G, Manji HK. 2004. In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3. Neuropsychopharmacology 29:32-38
84. Chalecka-Franaszek E, Chuang DM. 1999. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc. Natl. Acad. Sci. USA 96:8745-50
85. Beaulieu JM,Marion S, Rodriguiz RM,Medvedev IO, Sotnikova TD, et al. 2008. A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell 132:125-36
86. De Sarno P, Li X, Jope RS. 2002. Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology 43:1158-64
87. Cox C, Harrison-Read PE, Steinberg H, Tomkiewicz M. 1971. Lithium attenuates drug-induced hyperactivity in rats. Nature 232:336-38
88. Ong JC, Brody SA, Large CH, Geyer MA. 2005. An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition. J. Pharmacol. Exp. Ther. 315:1163-71
89. Chen G, Huang LD, Jiang YM, Manji HK. 1999. The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J. Neurochem. 72:1327-30
90. Gould TD, Manji HK. 2005. Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 30:1223-37
91. Li X, Bijur GN, Jope RS. 2002. Glycogen synthase kinase-3beta, mood stabilizers, and neuroprotection. Bipolar Disord. 4:137-44
92. Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, et al. 2008. Synergistic neuroprotective effects of lithium and valproic acid or other histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J. Neurosci. 28:2576-88
93. Cohen P, Frame S. 2001. The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2:769-76
94. Woodgett JR. 2001. Judging a protein by more than its name: GSK-3. Science STKE 2001:RE12
95. Murase S, Mosser E, Schuman EM. 2002. Depolarization drives beta-catenin into neuronal spines promoting changes in synaptic structure and function. Neuron 35:91-105
96. Yu X, Malenka RC. 2003. Beta-catenin is critical for dendritic morphogenesis. Nat. Neurosci. 6:1169-77
97. Doble BW, Woodgett JR. 2003. GSK-3: tricks of the trade for a multi-tasking kinase. J. Cell Sci. 116:1175-86
98. Gould TD, Einat H, O'Donnell KC, Picchini AM, Schloesser RJ, et al. 2007. β-Catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors. Neuropsychopharmacology 32:2173-83
99. Gould TD, O'Donnell KC, Picchini AM, Dow ER, Chen G, et al. 2008. Generation and behavioral characterization of beta-catenin forebrain-specific conditional knock-out mice. Behav. Brain Res. 189:117-25
100. Sharp FR, Tomitaka M, Bernaudin M, Tomitaka S. 2001. Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends Neurosci. 24:330-34
101. Mohn AR, Gainetdinov RR, Caron MG, Koller BH. 1999. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98:427-36
102. Gainetdinov RR, Mohn AR, Caron MG. 2001. Genetic animal models: focus on schizophrenia. Trends Neurosci. 24:527-33
103. Sheng M, Hoogenraad CC. 2007. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76:823-47
104. Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Cyr M, et al. 2004. Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 41:625-38
105. Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, et al. 2004. DARPP-32: an integrator of neurotransmission. Annu. Rev. Pharmacol. Toxicol. 44:269-96
106. Esteban JA, Shi SH, Wilson C, Nuriya M, Huganir RL, Malinow R. 2003. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nat. Neurosci. 6:136-43
107. Zhu LQ,Wang SH, Liu D, Yin YY, Tian Q, et al. 2007. Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments. J. Neurosci. 27:12211-20
108. Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, et al. 2008. The role of GSK-3 in synaptic plasticity. Br. J. Pharmacol. 153(Suppl. 1):S428-37
109. Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, et al. 2007. LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53:703-17
110. Chen P,Gu Z, Liu W,Yan Z. 2007. Glycogen synthase kinase 3 regulates N-methyl-D-aspartate receptor channel trafficking and function in cortical neurons. Mol. Pharmacol. 72:40-51
111. Yuan Q, Lin F, Zheng X, Sehgal A. 2005. Serotonin modulates circadian entrainment in Drosophila. Neuron 47:115-27
112. Lewy AJ, Lefler BJ, Emens JS, Bauer VK. 2006. The circadian basis of winter depression. Proc. Natl. Acad. Sci. USA 103:7414-19
113. Mansour HA,Wood J, Logue T, Chowdari KV, Dayal M, et al. 2006. Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. Genes Brain Behav. 5:150-57
114. Yujnovsky I, Hirayama J, Doi M, Borrelli E, Sassone-Corsi P. 2006. Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. Proc. Natl. Acad. Sci. USA 103:6386-91
115. Yin L,Wang J, Klein PS, Lazar MA. 2006. Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science 311:1002-5
116. Doi M, Yujnovsky I, Hirayama J, Malerba M, Tirotta E, et al. 2006. Impaired light masking in dopamine D2 receptor-null mice. Nat. Neurosci. 9:732-34
117. Iitaka C, Miyazaki K, Akaike T, Ishida N. 2005. A role for glycogen synthase kinase-3β in the mammalian circadian clock. J. Biol. Chem. 280:29397-402
118. Dummler B, Tschopp O, Hynx D, Yang ZZ, Dirnhofer S, Hemmings BA. 2006. Life with a single isoform of Akt: Mice lacking Akt2 and Akt3 are viable but display affected glucose homeostasis and growth deficiencies. Mol. Cell Biol 6:8042-51
119. Thiselton DL, Vladimirov VI, Kuo PH, McClay J, Wormley B, et al. 2008. AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families. Biol. Psychiatry 63:449-57
120. Bajestan SN, Sabouri AH, Nakamura M, Takashima H, Keikhaee MR, et al. 2006. Association of AKT1 haplotype with the risk of schizophrenia in Iranian population. Am. J. Med. Genet. B 141:383-86
121. Schwab SG, Hoefgen B, Hanses C, Hassenbach MB, Albus M,et al. 2005. Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families. Biol. Psychiatry 58:446-50
122. Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, et al. 2004. Association of AKT1 with schizophrenia confirmed in a Japanese population. Biol. Psychiatry 56:698-700
123. Xu MQ, Xing QH, Zheng YL, Li S, Gao JJ, et al. 2007. Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population. J. Clin. Psychiatry 68:1358-67
124. Kanakry CG, Li Z, Nakai Y, Sei Y,Weinberger DR. 2007. Neuregulin-1 regulates cell adhesion via an ErbB2/phosphoinositide-3 kinase/Akt-dependent pathway: potential implications for schizophrenia and cancer. PLoS ONE 2:e1369
125. Sei Y, Ren-Patterson R, Li Z, Tunbridge EM, Egan MF, et al. 2007. Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-O-methyltransferase gene polymorphisms. Mol. Psychiatry 12:946-57
126. Hashimoto R, Numakawa T, Ohnishi T, Kumamaru E, Yagasaki Y, et al. 2006. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum. Mol. Genet. 15:3024-33
127. Karege F, Perroud N, Burkhardt S, Schwald M, Ballmann E, et al. 2007. Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims. Biol. Psychiatry 61:240-45
128. Serretti A, Benedetti F, Mandelli L, Calati R, Caneva B, et al. 2008. Association between GSK-3beta -50T/C polymorphism and personality and psychotic symptoms in mood disorders. Psychiatry Res. 158:132-40
129. Adli M, Hollinde DL, Stamm T, Wiethoff K, Tsahuridu M, et al. 2007. Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta -50T/C single nucleotide polymorphism. Biol. Psychiatry 62:1295-302
130. Benedetti F, Serretti A, Colombo C, Lorenzi C,Tubazio V, Smeraldi E. 2004. A glycogen synthase kinase 3-beta promoter gene single nucleotide polymorphism is associated with age at onset and response to total sleep deprivation in bipolar depression. Neurosci. Lett. 368:123-26
131. Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, et al. 2003. Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder. Mol. Psychiatry 8:546-57
132. Ertley RN, Bazinet RP, Lee HJ, Rapoport SI, Rao JS. 2007. Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex. Biol. Psychiatry 61:246-49
133. Valenstein M, McCarthy JF, Austin KL, Greden JF, Young EA, Blow FC. 2006. What happened to lithium? Antidepressant augmentation in clinical settings. Am. J. Psychiatry 163:1219-25
134. Fienberg AA, Hiroi N, Mermelstein PG, Song W, Snyder GL, et al. 1998. DARPP-32: regulator of the efficacy of dopaminergic neurotransmission. Science 281:838-42
135. Sotnikova TD, Beaulieu JM, Barak LS, Wetsel WC, Caron MG, et al. 2005. Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease. PLoS Biol. 3:e271
136. Zhou QY, Palmiter RD. 1995. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83:1197-209
137. Sotnikova TD, Beaulieu JM, Gainetdinov RR, Caron MG. 2006. Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter. CNS Neurol. Disord. Drug Targets 5:45-56
138. Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L, et al. 2003. Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc. Natl. Acad. Sci. USA 100:10782-87
139. Gesty-Palmer D, Chen M, Reiter E, Ahn S, Nelson CD, et al. 2006. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J. Biol. Chem. 281:10856-64
140. Schmid CL, Raehal KM, Bohn LM. 2008. Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo. Proc. Natl. Acad. Sci. USA 105:1079-84
141. Valjent E, Pascoli V, Svenningsson P, Paul S, Enslen H, et al. 2005. Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc. Natl. Acad. Sci. USA 102:491-96
142. Masri B, Salahpour A, Didriksen M, Ghisi V, Beaulieu JM, et al. 2008. Antagonism of dopamine D2 receptor/β-arrestin 2 interaction is a common property of clinically effective antipsychotics. Proc. Natl. Acad. Sci. USA 105:13656-61