Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways

Abstract

Antidepressants are commonly used in the treatment of anxiety and depression, medical conditions that affect ~17-20% of the population. The clinical effects of antidepressants take several weeks to manifest, suggesting that these drugs induce adaptive changes in brain structures affected by anxiety and depression. In order to develop shorter-acting and more effective drugs for the treatment of anxiety and depression, it is important to understand how antidepressants bring about their beneficial effects. Recent reports suggest that antidepressants can induce neurogenesis in the adult brain, although the mechanisms involved are not clearly understood. In this review, we describe the different neurotransmitter systems that are affected by anxiety and depression and how they are modulated by antidepressant treatment with a focus on signaling molecules and pathways that are activated during neurotransmitter receptor induced neurogenesis.

Chronic Fluoxetine Bidirectionally Modulates Potentiating Effects of Serotonin on the Hippocampal Mossy Fiber Synaptic Transmission

“…The chronic treatment of animals with SSRIs or antidepressant drugs has diverse effects on the central serotonergic system (Stahl, 1998;Taylor et al, 2005). In the present study, the chronic fluoxetine treatment caused the bidirectional change in the 5-HT-induced potentiation: The potentiation induced by the lower concentrations of 5-HT was enhanced, whereas that induced by the higher concentration of 5-HT was reduced (Fig.…”

“…Although SSRIs are often considered as the first-line treatment for mood and anxiety disorders, there is substantial heterogeneity in responsiveness of patients to SSRIs (Papakostas et al, 2008), and cellular mechanisms underlying their therapeutic effects and side effects still remain mostly unknown. Because it generally takes several weeks for the therapeutic effects of SSRIs to develop, adaptive changes in the central serotonergic system and/or other signaling systems have been thought to be involved (Taylor et al, 2005). To reveal the mechanism of action of SSRIs, it would be of critical importance to investigate cellular and synaptic changes associated with behavioral effects of chronic SSRI treatments in detail using experimental animals.…”

Flight Initiation and Maintenance Deficits in Flies with Genetically Altered Biogenic Amine Levels

“…Furthermore, specific cognitive functions have been assigned to monoamine codes, such as that in flies OA mediates appetitive learning but dopamine mediates aversive learning (Schwaerzel et al, 2003;Riemensperger et al, 2005). In mammals, dysfunctions in monoamine neurotransmission are implicated in neurological disorders, including Parkinson's disease, schizophrenia, anxiety, and depression (Kobayashi, 2001;Taylor et al, 2005).…”

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

“…Thus, the current pharmacotherapy is based on the discovery of the enhancement of serotonergic and/or noradrenergic neurotransmission by either inhibiting the intracellular degradation of the monoamines with monoamine oxidase inhibitors or blocking their reuptake back into the 5-HT and/or NA nerve terminal by selective serotonin/norepinephrine reuptake inhibitors, or tricyclic antidepressants (see Fuxe et al, 1983d;Duman et al, 1997;Skolnick, 1999;Nestler et al, 2002;Manji et al, 2001;Nemeroff, 1998), that in turn lead to an increase of extracellular monoamines (Iversen, 2000;Taylor et al, 2005;Schloss and Henn, 2004).…”