The psychosocial stress continued throughout, the treatment period of 28 days. The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-33%) by stress, effects that were prevented by the simultaneous administration of tianeptine yielding normal values. In stressed animals treated with tianeptine, hippocampal volume increased above the small decrease produced by stress alone. While these effects of tianeptine are intriguing indeed, a detailed study using several different, classes

Inhibitors,research,lifescience,medical of antidepressants is clearly needed to determine the precise influence of antidepressants on dendritic remodeling and synaptic function. In toto, although some of the evidence is selleck correlational rather than clearly causal, the evidence indicates that BDNF is associated with an antidepressant response and its induction may represent a key strategy for developing novel antidepressant, medication. In Inhibitors,research,lifescience,medical this context, a subtle mechanism to facilitate antidepressant-induced increase in CREB/BDNF expression/function may be by the use of cAMP-specific PDE4 inhibitors. Indeed, the possibility that inhibitors Inhibitors,research,lifescience,medical of this enzyme

have antidepressant efficacy is supported by older studies with rolipram, a relatively selective inhibitor of PDE4. Rolipram is reported to have efficacy in clinical trials and in preclinical models of depression, but. it also produces intolerable nausea.7 Molecular cloning studies demonstrate that there are four separate PDE4 genes, three of which are expressed in brain (PDE4A, PDE4B, and PDE4D). Current, evidence suggests that. PDE4A and PDE4B may be relevant targets for development of selective inhibitors.7-10 Studies are Inhibitors,research,lifescience,medical currently underway in PDE4A, PDE4B, and PDE4D null mutant mice, as well as with more selective inhibitors, to further validate these PDE4 isozymes

as targets of antidepressant treatments.7-10 Mood stabilizers regulate the MAP kinase signaling cascade As discussed above, Inhibitors,research,lifescience,medical several endogenous growth factors – including nerve growth factor (NGF) and BDNF – exert many of their neurotrophic effects via the MAP kinase signaling cascade. In view of the important role of MAP kinases in mediating long-term neuroplastic events, Rutecarpine it, is noteworthy that, lithium and valproic acid (VPA), at therapeutically relevant concentrations, have recently been demonstrated to robustly activate the extracellular signal-regulated kinase (ERK) MAP kinase cascade in rat, FC and hippocampus, as well as in human neuroblastoma SH-SY5Y cells (Figure I).39,52,127-142 Since the ERK MAP kinases are known to mediate many of the effects of various neurotrophic factors and to promote neurite outgrowth,132,143 VPA’s effects on the morphology of human neuroblastoma cells have been examined in detail. Human neuroblastoma SH-SY5Y cells exposed to VPA (1.0 mM) in serum-free media for 5 days exhibited prominent, growth cones and dramatic neurite outgrowth.