PMID- 23872400 OWN - NLM STAT- MEDLINE DCOM- 20140702 LR - 20220410 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 719 IP - 1-3 DP - 2013 Nov 5 TI - Dopamine D(3) receptor as a new pharmacological target for the treatment of depression. PG - 25-33 LID - S0014-2999(13)00544-X [pii] LID - 10.1016/j.ejphar.2013.07.022 [doi] AB - A substantial proportion of depressed patients do not respond to current antidepressant drug therapies. So far, antidepressant drugs have been developed based on the "monoaminergic hypothesis" of depression, which considers a synaptic deficiency in 5-hydroxytryptamine (5-HT; serotonin) or noradrenaline as main cause. More recently, the dopaminergic system has been implicated in the efficacy of some antidepressants, such as desipramine, amineptine, nomifensine. Dysfunction of dopaminergic neurotransmission within the mesolimbic system may contribute to anhedonia, loss of motivation and psychomotor retardation in severe depressive disorders. Dopamine D3 receptor subtype is located both pre- and postsynaptically in brain areas regulating motivation and reward-related behavior and has been implicated in depression-like behaviors. Activity of mesolimbic dopamine neurons in the reward circuit is a key determinant of behavioral susceptibility/resilience to chronic stress, which plays a central role in the pathogenesis of depression. Dopamine D3 receptor expression and function are both down-regulated in stress and depression, and these changes are reversed by antidepressant treatments, suggesting that enhanced dopaminergic neurotransmission mediated by dopamine D3 receptor participates in adaptive changes related to antidepressant activity. Of note, brain derived neurotrophic factor (BDNF) controls the expression of the dopamine D3 receptor in some brain areas and BDNF induction by antidepressant treatments is related to their behavioral activity. A number of experimental drugs in pre-clinical or clinical development, including aripiprazole and cariprazine, may act as antidepressants because of their partial agonist activity at dopamine D3 receptors. These preclinical and clinical data are discussed in the present review. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Leggio, Gian Marco AU - Leggio GM AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy. FAU - Salomone, Salvatore AU - Salomone S AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy. FAU - Bucolo, Claudio AU - Bucolo C AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy. FAU - Platania, Chiara AU - Platania C AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy. FAU - Micale, Vincenzo AU - Micale V AD - CEITEC (Central European Institute of Technology) Masaryk University, Brno, Czech Republic. FAU - Caraci, Filippo AU - Caraci F AD - Department of Educational Sciences, University of Catania, Catania, Italy; IRCCS Associazione Oasi Maria S.S. - Institute for Research on Mental Retardation and Brain Aging, 94018 Troina, Enna, Italy. Electronic address: carafil@hotmail.com. FAU - Drago, Filippo AU - Drago F AD - Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130718 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Receptors, Dopamine D3) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Central Nervous System/drug effects/metabolism MH - Depression/*drug therapy/etiology/metabolism/microbiology MH - Dopamine/metabolism MH - Humans MH - Molecular Targeted Therapy/*methods MH - Receptors, Dopamine D3/*metabolism OTO - NOTNLM OT - Aripiprazole OT - Brain-derived neurotrophic factor OT - Depression OT - Dopamine D(3) receptor OT - Partial agonist OT - Treatment-resistant depression EDAT- 2013/07/23 06:00 MHDA- 2014/07/06 06:00 CRDT- 2013/07/23 06:00 PHST- 2013/04/27 00:00 [received] PHST- 2013/06/05 00:00 [revised] PHST- 2013/07/01 00:00 [accepted] PHST- 2013/07/23 06:00 [entrez] PHST- 2013/07/23 06:00 [pubmed] PHST- 2014/07/06 06:00 [medline] AID - S0014-2999(13)00544-X [pii] AID - 10.1016/j.ejphar.2013.07.022 [doi] PST - ppublish SO - Eur J Pharmacol. 2013 Nov 5;719(1-3):25-33. doi: 10.1016/j.ejphar.2013.07.022. Epub 2013 Jul 18.