PMID- 24020973
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20190911
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 14
IP  - 11
DP  - 2013 Oct
TI  - The monoaminergic tripartite synapse: a putative target for currently available 
      antidepressant drugs.
PG  - 1277-94
AB  - Antidepressant drugs such as the serotonin (5-HT)/norepinephrine (NE) and 
      dopamine (DA) reuptake inhibitors activate monoaminergic neurotransmission in 
      various brain regions, such as the amygdala, the frontal cortex or the 
      hippocampus. Although this property is well established, the post-synaptic 
      mechanisms by which these pharmacological agents exert therapeutic activity in 
      major depressive disorders (MDD) is not fully understood. Recent clinical and 
      preclinical studies have indicated that the density and reactivity of glia and 
      more particularly of astrocytes are reduced in MDD patients. These data along 
      with the fact that astrocytes express monoaminergic transporters and receptors 
      make these cells putative targets for antidepressant treatments. Accordingly, in 
      vitro evidence has demonstrated that the application of various classes of 
      antidepressant drugs on rodent primary astrocyte cultures elicits a wide spectrum 
      of responses, from the rise in cytosolic calcium concentrations, as a marker of 
      cellular activity, to the release of glucose metabolites, gliotransmitters and 
      neurotrophic factors. Remarkably, antidepressant drugs also attenuate the release 
      of inflammatory molecules from reactive astrocytes or microglia, suggesting that 
      part of the beneficial effects in depressed patients or animal models of 
      depression might result from the ability of antidepressants to regulate the 
      synthesis and release of psychoactive substances acting on both pre- and 
      post-synaptic neurons. Among the many long-term targets of antidepressant drugs, 
      brainderived neurotrophic factor (BDNF) has been well studied because of the 
      positive influence on adult hippocampal neurogenesis, synaptogenesis and the 
      local serotonergic tone. This review will illustrate how the concept of the 
      tripartite synapse, which is classically associated with different forms of 
      plasticity involving glutamate, could be expanded to the monoaminergic systems to 
      regulate antidepressant drug responses. The recent in vivo data supporting that 
      hippocampal astrocytes act in concert with neurons to release BDNF under 
      pharmacological conditions and thereby regulate different facets of 
      anxiolytic-/antidepressant-like activities through neurogenesis-dependent and 
      independent mechanisms will be emphasized.
FAU - Quesseveur, Gael
AU  - Quesseveur G
AD  - Laboratory of Neuropharmacology, EA3544, University of Paris X1, 92290 
      Chatenay-Malabry, Cedex, France. bruno.guiard@u-psud.fr.
FAU - Gardier, Alain M
AU  - Gardier AM
FAU - Guiard, Bruno P
AU  - Guiard BP
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Antidepressive Agents)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Biogenic Amine)
RN  - 0 (Receptors, Neurotransmitter)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Astrocytes/drug effects/*metabolism
MH  - Biogenic Monoamines/*metabolism
MH  - Depressive Disorder, Major/drug therapy/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - Nerve Growth Factors/metabolism
MH  - Receptors, Biogenic Amine/metabolism
MH  - Receptors, Neurotransmitter/metabolism
MH  - Synapses/*drug effects/metabolism/*physiology
MH  - Synaptic Transmission
EDAT- 2013/09/12 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/09/12 06:00
PHST- 2013/07/31 00:00 [received]
PHST- 2013/08/27 00:00 [revised]
PHST- 2013/08/27 00:00 [accepted]
PHST- 2013/09/12 06:00 [entrez]
PHST- 2013/09/12 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - CDT-EPUB-55598 [pii]
AID - 10.2174/13894501113149990209 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2013 Oct;14(11):1277-94. doi: 10.2174/13894501113149990209.