The Silvio O. Conte center dopamine dysfunction in Schizophrenia

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Relevant publications by Center Investigators


Overviews on dopamine transmission in schizophrenia

Abi-Dargham, A. (2004). Do we still believe in the dopamine hypothesis? New data bring new evidence. International Journal of Neuropsychopharmacology 7 Suppl 1, S1-5. PMID 14972078

Abi-Dargham, A. & Moore, H. (2003). Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia. Neuroscientist 9, 404-416. PMID 14580124

Freyberg, Z., Ferrando, S.J. & Javitch, J.A. (2010). Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. American Journal of Psychiatry 167, 388-396. PMID 19917593

Karam, C.S., Ballon, J.S., Bivens, N.M., Freyberg, Z., Girgis, R.R., Lizardi-Ortiz, J.E., Markx, S., Lieberman, J.A. & Javitch, J.A. (2010). Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. Trends in Pharmacological Sciences 31, 381-390. PMID 20579747

Laruelle, M. (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Research - Brain Research Reviews 31, 371-384. PMID 10719165

Lyon, G.J., Abi-Dargham, A., Moore, H., Lieberman, J.A., Javitch, J.A. & Sulzer, D. (2011). Presynaptic regulation of dopamine transmission in schizophrenia. Schizophrenia Bulletin 37, 108-117. PMID 19525353

Miyake, N., Thompson, J., Skinbjerg, M. & Abi-Dargham, A. (2011). Presynaptic dopamine in schizophrenia. CNS Neuroscience & Therapeutics 17, 104-109. PMID 21199451

Simpson, E.H., Kellendonk, C. & Kandel, E. (2010). A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65, 585-596. PMID 20223196

Urban, N. & Abi-Dargham, A. (2010). Neurochemical imaging in schizophrenia. Current Topics in Behavioral Neurosciences 4, 215-242. PMID 21312402

Simpson EH, Waltz JA, Kellendonk C, Balsam PD (2012). Schizophrenia in translation: dissecting motivation in schizophrenia and rodents. Schizophr Bull. 38(6):1111-7. PMID: 23015686

Brain imaging studies of dopamine function in schizophrenia


Abi-Dargham, A. & Laruelle, M. (2005). Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. European Psychiatry: the Journal of the Association of European Psychiatrists 20, 15-27. PMID 15642439

Abi-Dargham, A., van de Giessen, E., Slifstein, M., Kegeles, L.S. & Laruelle, M. (2009). Baseline and amphetamine-stimulated dopamine activity are related in drug-naive schizophrenic subjects. Biological Psychiatry 65, 1091-1093. PMID 19167701

Frankle, W.G., Gil, R., Hackett, E., Mawlawi, O., Zea-Ponce, Y., Zhu, Z., Kochan, L.D., Cangiano, C., Slifstein, M., Gorman, J.M., Laruelle, M. & Abi-Dargham, A. (2004). Occupancy of dopamine D2 receptors by the atypical antipsychotic drugs risperidone and olanzapine: theoretical implications. Psychopharmacology 175, 473-480. PMID 15083259

Kegeles, L.S., Slifstein, M., Frankle, W.G., Xu, X., Hackett, E., Bae, S.-A., Gonzales, R., Kim, J.-H., Alvarez, B., Gil, R., Laruelle, M. & Abi-Dargham, A. (2008). Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology 33, 3111-3125. PMID 18418366

Kegeles, L.S., Abi-Dargham, A., Frankle, W.G., Gil, R., Cooper, T.B., Slifstein, M., Hwang, D.-R., Huang, Y., Haber, S.N. & Laruelle, M. (2010). Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Archives of General Psychiatry 67, 231-239. PMID 20194823

Kegeles, L.S., Slifstein, M., Xu, X., Urban, N., Thompson, J.L., Moadel, T., Harkavy-Friedman, J.M., Gil, R., Laruelle, M. & Abi-Dargham, A. (2010). Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated with [18F]fallypride positron emission tomography. Biological Psychiatry 68, 634-641. PMID 20673873

Laruelle, M., Abi-Dargham, A., van Dyck, C.H., Gil, R., D'Souza, C.D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S.S., Baldwin, R.M., Seibyl, J.P., Krystal, J.H., Charney, D.S. & Innis, R.B. (1996). Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings of the National Academy of Sciences of the United States of America 93, 9235-9240. PMID 8799184

Slifstein, M., van de Giessen, E., VanSnellenberg, J., Thompson, J., Narendran, R., Gil, R., Hackett, E., Girgis, R., Ojeil, N., Moore, H., D'Souza, D., Malison, R., Huang, Y., Lim, K., Nabulsi, N., Carson, R., Lieberman, J., Abi-Dargham, A. (in press) Deficits in prefrontal cortical and extra-striatal dopamine release in schizophrenia: a PET fMRI study, JAMA Psychiatry

The neuroscience of cognition and impairments in schizophrenia


Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.-R., Keilp, J., Kochan, L., Van Heertum, R., Gorman, J.M. & Laruelle, M. (2002). Prefrontal dopamine D1 receptors and working memory in schizophrenia. Journal of Neuroscience 22, 3708-3719.PMID 11978847

Buchanan, R.W., Freedman, R., Javitt, D.C., Abi-Dargham, A. & Lieberman, J.A. (2007). Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophrenia Bulletin 33, 1120-1130.PMID 17641146

Carter, C.S., Barch, D.M., Buchanan, R.W., Bullmore, E., Krystal, J.H., Cohen, J., Geyer, M., Green, M., Nuechterlein, K.H., Robbins, T., Silverstein, S., Smith, E.E., Strauss, M., Wykes, T. & Heinssen, R. (2008). Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biological Psychiatry 64, 4-10.PMID 18466880

D'Esposito, M., Postle, B.R., Jonides, J. & Smith, E.E. (1999). The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI. Proceedings of the National Academy of Sciences of the United States of America 96, 7514-7519.PMID 10377446

Franklin, M.S., Smith, E.E. & Jonides, J. (2007). Distance effects in memory for sequences: evidence for estimation and scanning processes. Memory 15, 104-116.PMID 17479928

Marshuetz, C., Reuter-Lorenz, P.A., Smith, E.E., Jonides, J. & Noll, D.C. (2006). Working memory for order and the parietal cortex: an event-related functional magnetic resonance imaging study. Neuroscience 139, 311-316. PMID 16417974

Smith, E.E. & Grossman, M. (2008). Multiple systems of category learning. Neuroscience & Biobehavioral Reviews 32, 249-264.PMID 17904637

Smith, E.E., Eich, T.S., Cebenoyan, D. & Malapani, C. (2011). Intact and impaired cognitive-control processes in schizophrenia. Schizophrenia Research 126, 132-137.PMID 21211945

Sylvester, C.-Y.C., Wager, T.D., Lacey, S.C., Hernandez, L., Nichols, T.E., Smith, E.E. & Jonides, J. (2003). Switching attention and resolving interference: fMRI measures of executive functions. Neuropsychologia 41, 357-370. PMID 12457760

Xu, H., Kellendonk, C.B., Simpson, E.H., Keilp, J.G., Bruder, G.E., Polan, H.J., Kandel, E.R. & Gilliam, T.C. (2007). DRD2 C957T polymorphism interacts with the COMT Val158Met polymorphism in human working memory ability. Schizophrenia Research 90, 104-107. PMID 17113268

Kahn JB, Ward RD, Kahn LW, Rudy NM, Kandel ER, Balsam PD, Simpson EH.(2012). Medial prefrontal lesions in mice impair sustained attention but spare maintenance of information in working memory. Learn Mem.19(11):513-7. PMID: 23073640

Van Snellenberg, JX., Conway, A. R. A., Spicer, J., Read, C., & Smith, E. E. (2014). Capacity estimates in working memory: Reliability and interrelationships among tasks. Cognitive, Affective, and Behavioral Neuroscience, 14, 106-116. PMID: 24399681

The relevant brain circuitry


Calzavara, R., Mailly, P. & Haber, S.N. (2007). Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action. European Journal of Neuroscience 26, 2005-2024. PMID 17892479

Chuhma, N., Tanaka, K.F., Hen, R. & Rayport, S. (2011). Functional connectome of the striatal medium spiny neuron. Journal of Neuroscience 31, 1183-1192. PMID 21273403

Frankle, W.G., Laruelle, M. & Haber, S.N. (2006). Prefrontal cortical projections to the midbrain in primates: evidence for a sparse connection. Neuropsychopharmacology 31, 1627-1636. PMID 16395309

Haber, S.N., Kim, K.-S., Mailly, P. & Calzavara, R. (2006). Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. Journal of Neuroscience 26, 8368-8376. PMID 16899732

Haber, S.N. (2003). The primate basal ganglia: parallel and integrative networks. Journal of Chemical Neuroanatomy 26, 317-330. PMID 14729134

Haber, S.N. & Calzavara, R. (2009). The cortico-basal ganglia integrative network: the role of the thalamus. Brain Research Bulletin 78, 69-74. PMID 18950692

Haber, S.N. & Knutson, B. (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4-26. PMID 19812543

Chuhma N, Mingote S, Moore H, Rayport S (2014), Dopamine neurons control striatal cholinergic neurons via regionally heterogeneous dopamine and glutamate signaling. Neuron 81: 901-912. PMID 24559678

Cazorla, M, Delmondes de Carvalho FD, Chohan MO, Shegda M, Chuhma N, Rayport S, Ahmari SE, Moore H, Kellendonk C (2014) Dopamine D2 receptors regulate the anatomical balance of basal ganglia circuitry. Neuron, 81:153–164. PMID 24411738

Using animal models to understand dopamine dysfunction in schizophrenia


Bach, M.-E., Simpson, E.H., Kahn, L., Marshall, J.J., Kandel, E.R. & Kellendonk, C. (2008). Transient and selective overexpression of D2 receptors in the striatum causes persistent deficits in conditional associative learning. Proceedings of the National Academy of Sciences of the United States of America 105, 16027-16032. PMID 18832466

Drew, M.R., Simpson, E.H., Kellendonk, C., Herzberg, W.G., Lipatova, O., Fairhurst, S., Kandel, E.R., Malapani, C. & Balsam, P.D. (2007). Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. Journal of Neuroscience 27, 7731-7739. PMID 17634367

Gaisler-Salomon, I., Miller, G.M., Chuhma, N., Lee, S., Zhang, H., Ghoddoussi, F., Lewandowski, N., Fairhurst, S., Wang, Y., Conjard-Duplany, A., Masson, J., Balsam, P., Hen, R., Arancio, O., Galloway, M.P., Moore, H.M., Small, S.A. & Rayport, S. (2009). Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia. Neuropsychopharmacology 34, 2305-2322. PMID 19516252

Kellendonk, C. (2009). Modeling excess striatal D2 receptors in mice. Progress in Brain Research 179, 59-65. PMID 20302818

Kellendonk, C., Simpson, E.H., Polan, H.J., Malleret, G., Vronskaya, S., Winiger, V., Moore, H. & Kandel, E.R. (2006). Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron 49, 603-615. PMID 16476668

Kellendonk, C., Simpson, E.H. & Kandel, E.R. (2009). Modeling cognitive endophenotypes of schizophrenia in mice. Trends in Neurosciences 32, 347-358. PMID 19409625

Moore, H., Jentsch, J.D., Ghajarnia, M., Geyer, M.A. & Grace, A.A. (2006). A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia. Biological Psychiatry 60, 253-264. PMID 16581031

Moore, H. (2010). The role of rodent models in the discovery of new treatments for schizophrenia: updating our strategy. Schizophrenia Bulletin 36, 1066-1072. PMID 20870929

Ward, R.D., Kellendonk, C., Simpson, E.H., Lipatova, O., Drew, M.R., Fairhurst, S., Kandel, E.R. & Balsam, P.D. (2009). Impaired timing precision produced by striatal D2 receptor overexpression is mediated by cognitive and motivational deficits. Behavioral Neuroscience 123, 720-730. PMID 19634929

Simpson EH, Morud J, Winiger V, Biezonski D, Zhu JP, Bach ME, Malleret G, Polan HJ, Ng-Evans S, Phillips PE, Kellendonk C, Kandel ER. (2014) Genetic variation in COMT activity impacts learning and dopamine release capacity in the striatum. Learn Mem. Mar 17;21(4):205-14. PMID: 24639487

Simpson EH, Winiger V, Biezonski DK, Haq I, Kandel ER, Kellendonk C. (2013) Selective Overexpression of Dopamine D3 Receptors in the Striatum Disrupts Motivation but not Cognition. Biol Psychiatry. doi: 10.1016/j.biopsych.2013.11.023. [Epub ahead of print] PMID: 24387821

Trifilieff P, Feng B, Urizar E, Winiger V, Ward RD, Taylor KM, Martinez D, Moore H, Balsam PD, Simpson EH, Javitch JA. (2013) Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry. 18(9):1025-33. PMID: 23711983

Ward RD, Simpson EH, Richards VL, Deo G, Taylor K, Glendinning JI, Kandel ER, Balsam PD. (2012) Dissociation of hedonic reaction to reward and incentive motivation inan animal model of the negative symptoms of schizophrenia. Neuropsychopharmacology. 37(7):1699-707. PMID: 22414818

Simpson EH, Kellendonk C, Ward RD, Richards V, Lipatova O, Fairhurst S, Kandel ER, Balsam PD. (2011) Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia. Biol Psychiatry. 69(10):928-35. PMID: 21414604

Li YC, Kellendonk C, Simpson EH, Kandel ER, Gao WJ (2011) D2 receptor overexpression in the striatum leads to a deficit in inhibitory transmission and dopamine sensitivity in mouse prefrontal cortex. Proc Natl Acad Sci U S A. 108(29):12107-12. Erratum in: Proc Natl Acad Sci U S A. 2013, 110(11):4429. PubMed PMID: 21730148

Cazorla M, Shegda M, Ramesh B, Harrison NL, Kellendonk C. (2012) Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via Kir2 channels. J Neurosci. 32(7):2398-409. PMID: 22396414

Basic studies on dopamine transmission and the mechanisms underlying the actions of therapeutic drugs: from cells to humans


Chien, E.Y.T., Liu, W., Zhao, Q., Katritch, V., Han, G.W., Hanson, M.A., Shi, L., Newman, A.H., Javitch, J.A., Cherezov, V. & Stevens, R.C. (2010). Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091-1095. PMID 21097933

Floresco, S.B., West, A.R., Ash, B., Moore, H. & Grace, A.A. (2003). Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission. Nature Neuroscience 6, 968-973. PMID 12897785

Geldwert, D., Norris, J.M., Feldman, I.G., Schulman, J.J., Joyce, M.P. & Rayport, S. (2006). Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA synapses in vitro. BMC Neuroscience 7, 53. PMID 16813648

Goodwin, J.S., Larson, G.A., Swant, J., Sen, N., Javitch, J.A., Zahniser, N.R., De Felice, L.J. & Khoshbouei, H. (2009). Amphetamine and methamphetamine differentially affect dopamine transporters in vitro and in vivo. Journal of Biological Chemistry 284, 2978-2989. PMID 19047053

Guo, N., Guo, W., Kralikova, M., Jiang, M., Schieren, I., Narendran, R., Slifstein, M., Abi-Dargham, A., Laruelle, M., Javitch, J.A. & Rayport, S. (2010). Impact of D2 receptor internalization on binding affinity of neuroimaging radiotracers. Neuropsychopharmacology 35, 806-817. PMID 19956086

Guo, W., Urizar, E., Kralikova, M., Mobarec, J.C., Shi, L., Filizola, M. & Javitch, J.A. (2008). Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO Journal 27, 2293-2304. PMID 18668123

Guptaroy, B., Zhang, M., Bowton, E., Binda, F., Shi, L., Weinstein, H., Galli, A., Javitch, J.A., Neubig, R.R. & Gnegy, M.E. (2009). A juxtamembrane mutation in the N terminus of the dopamine transporter induces preference for an inward-facing conformation. Molecular Pharmacology 75, 514-524. PMID 19098122

Han, Y., Moreira, I.S., Urizar, E., Weinstein, H. & Javitch, J.A. (2009). Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nature Chemical Biology 5, 688-695. PMID 19648932

Mizuno, T., Schmauss, C. & Rayport, S. (2007). Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens. BMC Neuroscience 8, 8. PMID 17239247

Namkung, Y., Dipace, C., Javitch, J.A. & Sibley, D.R. (2009). G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor. Journal of Biological Chemistry 284, 15038-15051. PMID 19332542

Slifstein, M., Suckow, R.F., Javitch, J.A., Cooper, T., Lieberman, J. & Abi-Dargham, A. (2011). Characterization of in vivo pharmacokinetic properties of the dopamine D1 receptor agonist DAR-0100A in nonhuman primates using PET with [11C] NNC112 and [11C] raclopride. Journal of Cerebral Blood Flow & Metabolism 31, 293-304. PMID 20571519

Zhao, Y., Terry, D.S., Shi, L., Quick, M., Weinstein, H., Blanchard, S.C. & Javitch, J.A. (2011). Substrate-modulated gating dynamics in a Na+-coupled neurotransmitter transporter homologue. Nature 474, 109-113. PMID 21516104

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