Review Article

Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication

Table 2

Involvement of cAMP, Wnt/ -catenin, and mTOR-signaling pathways in major depression (MDD) and antidepressant treatment.

Signaling pathwaysChanges related to disease or treatmentDirect effect
Nontreated MDD (versus control)Treated MDD (versus untreated)
Change RegionReferenceChangeRegionReferenceChangeReference

cAMP/PKA cAMP AC (induced by FK, -AR, -AR) [8794] cAMP [95, 96]
5-HT1A-induced AC inhibition/ 5-HT4-induced AC stimulationHuman PFCx[8, 97, 98]cAMP (administration/degradation inhibition) AD-like effect[99]
       ↑ AC CB1-induced inhibition [100]    
PKANo data ↑ PKA activity [101]No data
CREB CREB [102104] ↑ CREB (protein, expression, activity) Hp, Cx  [11, 103110]  CREB viral expression in Hp AD-like effect[44]
CREB viral expression in Acb depression-like effect[111]
Epac Epac- Hp, PFCx [112] No data No data

Wnt/ -catenin   GSK- GSK-  Hp   [113] GSK-3β   Hp  [8, 10, 113117]   GSK-3 inhibition AD-like and anxiolytic effect  [117120]
GSK-3 knock in stress-induced depression[121]
GSK-3β SNP ( T/C; rs334558) later onset of bipolar depression[122]
GSK-3β SNP ( T/C; rs334558)
antidepressant response
[123]
-catenin β-catenin PFCx [124] -catenin Hp[8, 10, 26, 83, 113117] -catenin ko mice depression-like effect[125]
-catenin OE mice AD-like effect[126]

mTORmTOR mTOR, p70S6K, eIF4B, p-eIF4B [127129] p-mTOR/mTORPFCx [27, 130]Activation (NMDAr antagonists) AD-like effect[27, 131]

: increase; : decrease; AC: adenylyl cyclase activity; FK: forskolin; Hp: hippocampus; PFCx: prefrontal cortex; Acb: accumbens nucleus; OE: overexpressing.