Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 25-33 |
| Number of pages | 9 |
| Journal | European Journal of Pharmacology |
| Volume | 719 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- Aripiprazole
- Brain-derived neurotrophic factor
- Depression
- Dopamine D receptor
- Partial agonist
- Treatment-resistant depression
ASJC Scopus subject areas
- Pharmacology
Cite this
Dopamine D3 receptor as a new pharmacological target for the treatment of depression. / Leggio, Gian Marco; Salomone, Salvatore; Bucolo, Claudio; Platania, Chiara; Micale, Vincenzo; Caraci, Filippo; Drago, Filippo.
In: European Journal of Pharmacology, Vol. 719, No. 1-3, 2013, p. 25-33.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dopamine D3 receptor as a new pharmacological target for the treatment of depression
AU - Leggio, Gian Marco
AU - Salomone, Salvatore
AU - Bucolo, Claudio
AU - Platania, Chiara
AU - Micale, Vincenzo
AU - Caraci, Filippo
AU - Drago, Filippo
PY - 2013
Y1 - 2013
N2 - 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.
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.
KW - Aripiprazole
KW - Brain-derived neurotrophic factor
KW - Depression
KW - Dopamine D receptor
KW - Partial agonist
KW - Treatment-resistant depression
UR - http://www.scopus.com/inward/record.url?scp=84888286535&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84888286535&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2013.07.022
DO - 10.1016/j.ejphar.2013.07.022
M3 - Article
C2 - 23872400
AN - SCOPUS:84888286535
VL - 719
SP - 25
EP - 33
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -