Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine

Abstract

Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the antidepressant, tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl) amino]-7 heptanoic acid, sodium salt), a compound with structural similarities to the tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of tianeptine involve the dynamic interplay between numerous neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of tianeptine on central plasticity is the most thoroughly studied of any antidepressants. Effects of tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of tianeptine as an antidepressant, these actions offer insights into how compounds like tianeptine may be useful in the treatment of neurobiological features of depressive disorders. Molecular Psychiatry (2005) 10, 525-537.

p21 Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus

“…These proinflammatory cytokines activate the Jak-STAT signaling pathway (41), and several binding sites for STAT1 and STAT3 are present on the p21 promoter (37). Antidepressants might indirectly reduce p21 levels by decreasing hypothalamo-pituitary-adrenal axis activity (42,43) or by restraining the expression of inflammatory cytokines (44).…”

Advances in the treatment of anxiety: Targeting glutamate

“…5) Rationally based treatment: Our current first line medications for anxiety and depression are mostly reiterations of treatments discovered by serendipity (i.e., multiple classes of medications targeting the brain monoamine systems). 22,23 Almost none was developed based on molecular or preclinical neuroscience. Hence, we cannot assert that any of our current treatments actually target a known pathophysiology related to anxiety, frustrating our ability to make progress in developing more effective medications.…”

Long-Term Behavioral Changes After Cessation of Chronic Antidepressant Treatment in Olfactory Bulbectomized Rats

“…Jancsar and Leonard (1984) hypothesized that OBXinduced structural alterations in the locus coeruleus and raphe nuclei might account for these catecholaminergic and serotonergic dysfunctions. Olfactory bulb ablation also leads to enlarged lateral and 3rd ventricles as well as decreased hippocampal volume, which can also be observed in depressed humans (McEwen and Olie 2005;Sheline 2003). Ablation of the bulbs also results in several behavioral changes in rats, including increased hyperactivity in a novel environment, deficits in passive-avoidance learning, and anhedonia (Kelly et al 1997;Wieronska et al 2001).…”