Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function.
The hippocampus plays an important role in emotional and cognitive processing, and both of these domains are affected in patients with major depressive disorder (MDD). Extensive preclinical research and the notion that modulation of serotonin (5-HT) neurotransmission plays a key role in the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs) support the view that 5-HT is important for hippocampal function in normal and disease-like conditions. The hippocampus is densely innervated by serotonergic fibers, and the majority of 5-HT receptor subtypes are expressed there. Furthermore, hippocampal cells often co-express multiple 5-HT receptor subtypes that can have either complementary or opposing effects on cell function, adding to the complexity of 5-HT neurotransmission. Here we review the current knowledge of how 5-HT, through its various receptor subtypes, modulates hippocampal output and the activity of hippocampal pyramidal cells in rodents. In addition, we discuss the relevance of 5-HT modulation for cognitive processing in rodents and possible clinical implications of these results in patients with MDD. Finally, we review the data on how SSRIs and vortioxetine, an antidepressant with multimodal activity, affect hippocampal function, including cognitive processing, from both a preclinical and clinical perspective.
1Lundbeck Research USA,Paramus,New Jersey,USA.
Elena
E
Dale
1Lundbeck Research USA,Paramus,New Jersey,USA.
Alan L
AL
Pehrson
1Lundbeck Research USA,Paramus,New Jersey,USA.
Theepica
T
Jeyarajah
1Lundbeck Research USA,Paramus,New Jersey,USA.
Yan
Y
Li
1Lundbeck Research USA,Paramus,New Jersey,USA.
Steven C
SC
Leiser
1Lundbeck Research USA,Paramus,New Jersey,USA.
Gennady
G
Smagin
2Lundbeck DK,Copenhagen-Valby,Denmark.
Christina K
CK
Olsen
1Lundbeck Research USA,Paramus,New Jersey,USA.
Connie
C
Sanchez
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009435:Synaptic Transmission
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
Hippocampus; SSRI; pyramidal cell; serotonin; vortioxetine