Biesdorf, C, Wang, AL, Topic, B, et al. Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction. Neurobiol Learn Mem. 2015; 123: 125–139.
Cools, R, D’Esposito, M. Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry. 2011; 69(12): e113–e125.
Hamid, AA, Pettibone, JR, Mabrouk, OS, et al. Mesolimbic dopamine signals the value of work. Nat Neurosci. 2016; 19(1): 117–126.
Kegeles, LS, Abi-Dargham, A, Frankle, WG, et al. Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch Gen Psychiatry. 2010; 67(3): 231–239.
Gingrich, JA, Caron, MG. Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci. 1993; 16: 299–321.
Sibley, DR, Monsma, FJ Jr. Molecular biology of dopamine receptors. Trends Pharmacol Sci. 1992; 13(2): 61–69.
Beaulieu, JM, Gainetdinov, RR, Caron, MG. The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci. 2007; 28(4): 166–172.
Leucht, S, Davis, JM. Schizophrenia, primary negative symptoms, and soft outcomes in psychiatry. Lancet. 2017; 389(10074): 1077–1078.
Potkin, SG, Loze, JY, Forray, C, et al. Multidimensional assessment of functional outcomes in schizophrenia: results from QUALIFY, a head-to-head trial of aripiprazole once-monthly and paliperidone palmitate. Int J Neuropsychopharmacol. 2017; 20(1): 40–49.
Nemeth, G, Laszlovszky, I, Czobor, P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial. Lancet. 2017; 389(10074): 1103–1113.
Tsapakis, EM, Dimopoulou, T, Tarazi, FI. Clinical management of negative symptoms of schizophrenia: an update. Pharmacol Ther. 2015; 153: 135–147.
Sokoloff, P, Giros, B, Martres, MP, Bouthenet, ML, Schwartz, JC. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990; 347(6289): 146–151.
Gurevich, EV, Joyce, JN. Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons. Neuropsychopharmacology. 1999; 20(1): 60–80.
Sokoloff, P, Le Foll, B. The dopamine D3 receptor, a quarter century later. Eur J Neurosci. 2017; 45(1): 2–19.
Sokoloff, P, Diaz, J, Le Foll, B, et al. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets. 2006; 5(1): 25–43.
Stahl, SM. Dazzled by the dominions of dopamine: clinical roles of D3, D2, and D1 receptors. CNS Spectr. 2017; 22(4): 305–311.
Grace, AA. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci. 2016; 17(8): 524–532.
Kapur, S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. 2003; 160(1): 13–23.
Maggio, R, Scarselli, M, Capannolo, M, Millan, MJ. Novel dimensions of D3 receptor function: focus on heterodimerisation, transactivation and allosteric modulation. Eur Neuropsychopharmacol. 2015; 25(9): 1470–1479.
Scarselli, M, Novi, F, Schallmach, E, et al. D2/D3 dopamine receptor heterodimers exhibit unique functional properties. J Biol Chem. 2001; 276(32): 30308–30314.
Fiorentini, C, Busi, C, Spano, P, Missale, C. Role of receptor heterodimers in the development of L-dopa-induced dyskinesias in the 6-hydroxydopamine rat model of Parkinson’s disease. Parkinsonism Relat Disord. 2008; 14(Suppl 2): S159–S164.
Marcellino, D, Ferre, S, Casado, V, et al. Identification of dopamine D1-D3 receptor heteromers. Indications for a role of synergistic D1-D3 receptor interactions in the striatum. J Biol Chem. 2008; 283(38): 26016–26025.
Torvinen, M, Marcellino, D, Canals, M, et al. Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Mol Pharmacol. 2005; 67(2): 400–407.
Collo, G, Bono, F, Cavalleri, L, et al. Nicotine-induced structural plasticity in mesencephalic dopaminergic neurons is mediated by dopamine D3 receptors and Akt-mTORC1 signaling. Mol Pharmacol. 2013; 83(6): 1176–1189.
Cussac, D, Newman-Tancredi, A, Pasteau, V, Millan, MJ. Human dopamine D(3) receptors mediate mitogen-activated protein kinase activation via a phosphatidylinositol 3-kinase and an atypical protein kinase C-dependent mechanism. Mol Pharmacol. 1999; 56(5): 1025–1030.
Collo, G, Zanetti, S, Missale, C, Spano, P. Dopamine D3 receptor-preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal-regulated kinase phosphorylation. Eur J Neurosci. 2008; 28(7): 1231–1240.
Schwartz, JC, Diaz, J, Pilon, C, Sokoloff, P. Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions. Brain Res Brain Res Rev. 2000; 31(2-3): 277–287.
Gyertyan, I, Saghy, K. Effects of dopamine D3 receptor antagonists on spontaneous and agonist-reduced motor activity in NMRI mice and Wistar rats: comparative study with nafadotride, U 99194A and SB 277011. Behav Pharmacol. 2004; 15(4): 253–262.
Nakajima, S, Gerretsen, P, Takeuchi, H, et al. The potential role of dopamine D(3) receptor neurotransmission in cognition. Eur Neuropsychopharmacol. 2013; 23(8): 799–813.
Barth, V, Need, AB, Tzavara, ET, et al. In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder. J Pharmacol Exp Ther. 2013; 344(2): 501–510.
Laszy, J, Laszlovszky, I, Gyertyan, I. Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats. Psychopharmacology (Berl). 2005; 179(3): 567–575.
Millan, MJ, Di Cara, B, Dekeyne, A, et al. Selective blockade of dopamine D(3) versus D(2) receptors enhances frontocortical cholinergic transmission and social memory in rats: a parallel neurochemical and behavioural analysis. J Neurochem. 2007; 100(4): 1047–1061.
Watson, DJ, Loiseau, F, Ingallinesi, M, Millan, MJ, Marsden, CA, Fone, KC. Selective blockade of dopamine D3 receptors enhances while D2 receptor antagonism impairs social novelty discrimination and novel object recognition in rats: a key role for the prefrontal cortex. Neuropsychopharmacology. 2012; 37(3): 770–786.
Lumme, V, Aalto, S, Ilonen, T, Nagren, K, Hietala, J. Dopamine D2/D3 receptor binding in the anterior cingulate cortex and executive functioning. Psychiatry Res. 2007; 156(1): 69–74.
Simpson, EH, Winiger, V, Biezonski, DK, Haq, I, Kandel, ER, Kellendonk, C. Selective overexpression of dopamine D3 receptors in the striatum disrupts motivation but not cognition. Biol Psychiatry. 2014; 76(10): 823–831.
Gross, G, Wicke, K, Drescher, KU. Dopamine D(3) receptor antagonism--still a therapeutic option for the treatment of schizophrenia. Naunyn Schmiedebergs Arch Pharmacol. 2013; 386(2): 155–166.
Joyce, JN, Millan, MJ. Dopamine D3 receptor antagonists as therapeutic agents. Drug Discov Today. 2005; 10(13): 917–925.
Van Kampen, JM, Eckman, CB. Dopamine D3 receptor agonist delivery to a model of Parkinson’s disease restores the nigrostriatal pathway and improves locomotor behavior. J Neurosci. 2006; 26(27): 7272–7280.
Mailman, RB, Murthy, V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des. 2010; 16(5): 488–501.
Pich, EM, Collo, G. Pharmacological targeting of dopamine D3 receptors: possible clinical applications of selective drugs. Eur Neuropsychopharmacol. 2015; 25(9): 1437–1447.
Frankel, JS, Schwartz, TL. Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole. Ther Adv Psychopharmacol. 2017; 7(1): 29–41.
Miyamoto, S, Duncan, GE, Marx, CE, Lieberman, JA. Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry. 2005; 10(1): 79–104.
Kiss, B, Horvath, A, Nemethy, Z, et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010; 333(1): 328–340.
Veselinovic, T, Paulzen, M, Grunder, G. Cariprazine, a new, orally active dopamine D2/3 receptor partial agonist for the treatment of schizophrenia, bipolar mania and depression. Expert Rev Neurother. 2013; 13(11): 1141–1159.
Goff, DC. Brexpiprazole: a new antipsychotic following in the footsteps of aripiprazole. Am J Psychiatry. 2015; 172(9): 820–821.
Stahl, SM. Drugs for psychosis and mood: unique actions at D3, D2, and D1 dopamine receptor subtypes. CNS Spectr. 2017; 22(5): 375–384.
Nakamura, T, Kubota, T, Iwakaji, A, Imada, M, Kapas, M, Morio, Y. Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). Drug Des Devel Ther. 2016; 10: 327–338.
Garnock-Jones, KP. Cariprazine: a review in schizophrenia. CNS Drugs. 2017; 31(6): 513–525.
De Berardis, D, Orsolini, L, Iasevoli, F, et al. The novel antipsychotic cariprazine (RGH-188): State-of-the-art in the treatment of psychiatric disorders. Curr Pharm Des. 2016; 22(33): 5144–5162.
Calabrese, JR, Keck, PE Jr., Starace, A, et al. Efficacy and safety of low- and high-dose cariprazine in acute and mixed mania associated with bipolar I disorder: a double-blind, placebo-controlled study. J Clin Psychiatry. 2015; 76(3): 284–292.
Durgam, S, Cutler, AJ, Lu, K, et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015; 76(12):e1574–e1582.
Durgam, S, Greenberg, WM, Li, D, et al. Safety and tolerability of cariprazine in the long-term treatment of schizophrenia: results from a 48-week, single-arm, open-label extension study. Psychopharmacology (Berl). 2017; 234(2): 199–209.
Durgam, S, Starace, A, Li, D, et al. An evaluation of the safety and efficacy of cariprazine in patients with acute exacerbation of schizophrenia: a phase II, randomized clinical trial. Schizophr Res. 2014; 152(2-3): 450–457.
Kane, JM, Zukin, S, Wang, Y, et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: Results from an international, phase III clinical trial. J Clin Psychopharmacol. 2015; 35(4): 367–373.
Cutler, AJ, Durgam, S, Wang, Y, et al. Evaluation of the long-term safety and tolerability of cariprazine in patients with schizophrenia: results from a 1-year open-label study. CNS Spectr. 2017: 1–12.
Ketter, TA, Sachs, GS, Durgam, S, et al. The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study. J Affect Disord. 2018; 225: 350–356.
Earley, W, Durgam, S, Lu, K, Laszlovszky, I, Debelle, M, Kane, JM. Safety and tolerability of cariprazine in patients with acute exacerbation of schizophrenia: a pooled analysis of four phase II/III randomized, double-blind, placebo-controlled studies. Int Clin Psychopharmacol. 2017; 32(6): 319–328.
Nasrallah, HA, Earley, W, Cutler, AJ, et al. The safety and tolerability of cariprazine in long-term treatment of schizophrenia: a post hoc pooled analysis. BMC Psychiatry. 2017; 17(1): 305.
Buchanan, RW, Breier, A, Kirkpatrick, B, Ball, P, Carpenter, WT, Jr. Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry. 1998; 155(6): 751–760.
Nemeth, B, Molnar, A, Akehurst, R, et al. Quality-adjusted life year difference in patients with predominant negative symptoms of schizophrenia treated with cariprazine and risperidone. J Comp Eff Res. 2017; 6(8): 639–648.
Choi, YK, Adham, N, Kiss, B, Gyertyan, I, Tarazi, FI. Long-term effects of cariprazine exposure on dopamine receptor subtypes. CNS Spectr. 2014; 19(3): 268–277.
Tarazi, FI, Florijn, WJ, Creese, I. Differential regulation of dopamine receptors after chronic typical and atypical antipsychotic drug treatment. Neuroscience. 1997; 78(4): 985–996.
Tarazi, FI, Yeghiayan, SK, Baldessarini, RJ, Kula, NS, Neumeyer, JL. Long-term effects of S(+)N-n-propylnorapomorphine compared with typical and atypical antipsychotics: differential increases of cerebrocortical D2-like and striatolimbic D4-like dopamine receptors. Neuropsychopharmacology. 1997; 17(3): 186–196.
Tarazi, FI, Zhang, K, Baldessarini, RJ. Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: implications for antipsychotic drug treatment. J Pharmacol Exp Ther. 2001; 297(2): 711–717.
Tarazi, FI, Moran-Gates, T, Wong, EH, Henry, B, Shahid, M. Differential regional and dose-related effects of asenapine on dopamine receptor subtypes. Psychopharmacology (Berl). 2008; 198(1): 103–111.
Gyertyan, I, Kiss, B, Saghy, K, et al. Cariprazine (RGH-188), a potent D3/D2 dopamine receptor partial agonist, binds to dopamine D3 receptors in vivo and shows antipsychotic-like and procognitive effects in rodents. Neurochem Int. 2011; 59(6): 925–935.
Zhang, K, Weiss, NT, Tarazi, FI, Kula, NS, Baldessarini, RJ. Effects of alkylating agents on dopamine D(3) receptors in rat brain: selective protection by dopamine. Brain Res. 1999; 847(1): 32–37.
Harvey, PD, Wingo, AP, Burdick, KE, Baldessarini, RJ. Cognition and disability in bipolar disorder: lessons from schizophrenia research. Bipolar Disord. 2010; 12(4): 364–375.
Baldessarini, RJ, Tarazi, FI. Pharmacotherapy of psychosis and mania. In: Brunton, LL, Lazo, JS, Parker, KL, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill; 2005:461–500.
Citrome, L. Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013; 30(2): 114–126.
Citrome, L. Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013; 30(2): 102–113.
Choi, YK, Adham, N, Kiss, B, Gyertyan, I, Tarazi, FI. Long-term effects of aripiprazole exposure on monoaminergic and glutamatergic receptor subtypes: comparison with cariprazine. CNS Spectr. 2017: 1–11.
Tarazi, FI, Zhang, K, Baldessarini, RJ. Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions. Psychopharmacology (Berl). 2002; 161(3): 263–270.
Tarazi, FI, Baldessarini, RJ, Kula, NS, Zhang, K. Long-term effects of olanzapine, risperidone, and quetiapine on ionotropic glutamate receptor types: implications for antipsychotic drug treatment. J Pharmacol Exp Ther. 2003; 306(3): 1145–1151.
Tarazi, FI, Choi, YK, Gardner, M, Wong, EH, Henry, B, Shahid, M. Asenapine exerts distinctive regional effects on ionotropic glutamate receptor subtypes in rat brain. Synapse. 2009; 63(5): 413–420.
Tarazi, FI, Florijn, WJ, Creese, I. Regulation of ionotropic glutamate receptors following subchronic and chronic treatment with typical and atypical antipsychotics. Psychopharmacology (Berl). 1996; 128(4): 371–379.
Tarsy, D, Baldessarini, RJ, Tarazi, FI. Effects of newer antipsychotics on extrapyramidal function. CNS Drugs. 2002; 16(1): 23–45.
Tsai, G, Coyle, JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol. 2002; 42: 165–179.
Zimnisky, R, Chang, G, Gyertyan, I, Kiss, B, Adham, N, Schmauss, C. Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse. Psychopharmacology (Berl). 2013; 226(1): 91–100.
Barnes, SA, Young, JW, Markou, A, Adham, N, Gyertyan, I, Kiss, B. The effects of cariprazine and aripiprazole on PCP-induced deficits on attention assessed in the 5-choice serial reaction time task. Psychopharmacology (Berl). 2018; 235(5): 1403–1414.
Neill, JC, Grayson, B, Kiss, B, Gyertyan, I, Ferguson, P, Adham, N. Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology. Eur Neuropsychopharmacol. 2016; 26(1): 3–14.
Reinwald, JR, Becker, R, Mallien, AS, et al. Neural mechanisms of early-life social stress as a developmental risk factor for severe psychiatric disorders. Biol Psychiatry. 2017.
Watson, DJG, King, MV, Gyertyan, I, Kiss, B, Adham, N, Fone, KCF. The dopamine D(3)-preferring D(2)/D(3) dopamine receptor partial agonist, cariprazine, reverses behavioural changes in a rat neurodevelopmental model for schizophrenia. Eur Neuropsychopharmacol. 2016; 26(2): 208–224.
Duric, V, Banasr, M, Franklin, T, et al. Cariprazine exhibits anxiolytic and dopamine D3 receptor-dependent antidepressant effects in the chronic stress model. Int J Neuropsychopharmacol. 2017; 20(10): 788–796.
Papp, M, Gruca, P, Lason-Tyburkiewicz, M, Adham, N, Kiss, B, Gyertyan, I. Attenuation of anhedonia by cariprazine in the chronic mild stress model of depression. Behav Pharmacol. 2014; 25(5-6): 567–574.
Chourbaji, S, Brandwein, C, Vogt, MA, et al. Dopamine receptor 3 (D3) knockout mice show regular emotional behaviour. Pharmacol Res. 2008; 58(5-6): 302–307.
Leggio, GM, Micale, V, Drago, F. Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). Eur Neuropsychopharmacol. 2008; 18(4): 271–277.
Meltzer, HY, Huang, M, He, W, Kiss, B, Farkas, B, Adham, N. Cariprazine enhances monoaminergic activity in the hippocampus and ventral striatum of rats: A possible basis for its antipsychotic effect. Biol Psychiatry 2018; 83(9, supplement): S228.