5‐HT₇, NEUROGENESIS AND ANTIDEPRESSANTS: A PROMISING THERAPEUTIC AXIS FOR TREATING DEPRESSION

Abstract

SUMMARY1. There is mounting evidence that a wide range of antidepressants share the common feature of increasing hippocampal neurogenesis. The specificity of this association has suggested that an ability to increase neurogenesis might be a useful paradigm to screen for compounds with antidepressant activity.2. The hope of developing better antidepressants has stimulated research into the molecular control of neurogenesis and here we summarize some of the recent findings. We also review recent work that highlights 5-HT 7 receptor as a promising molecular target in the treatment of depression.3. In summary, it appears that 5-HT 7 antagonism is capable of producing diverse antidepressant-like behavioural effects, alters hippocampal neuronal morphology and synergistically regulates hippocampal neurogenesis.

Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo

“…Furthermore, 5-HT 7 −/− mice spend less time in REM sleep (Hedlund et al 2005). Finally, there is some evidence that 5-HT 7 receptor antagonism may affect neuronal morphology (Kvachnina et al 2005) and stimulate hippocampal neurogenesis alone (Nandam et al 2007), (Kodama et al 2004) or synergistically with another antidepressant (Xu et al 2006). This is consist with antidepressant activity, since antidepressant efficacy has been correlated with hippocampal neurogenesis in some (Santarelli et al 2003), (Malberg et al 2000), but not all (Holick et al 2008), studies.…”

Bi-directional modulation of bed nucleus of stria terminalis neurons by 5-HT: molecular expression and functional properties of excitatory 5-HT receptor subtypes

“…In vivo studies with 5-HT 7 receptor antagonists, such as SB 269970, have revealed a potential role for 5-HT 7 receptor activation in novel object recognition (Ballaz et al, 2007), stereotypic behavior (Hedlund and Sutcliffe, 2007), as well as anxiogenic and depressive-like behavior (Wesolowska et al, 2006, Nandam et al, 2007). Moreover, 5-HT 7 knockout mice exhibit impaired contextual fear conditioning (Roberts et al, 2004), and decreased immobility in the Porsolt swim test (Guscott et al, 2005).…”

The preclinical profile of lurasidone: clinical relevance for the treatment of schizophrenia

“…Lurasidone's high affinity and antagonistic activity at 5-HT 7 receptors may support its utility in the treatment of major depressive disorders (MDD) or in the treatment of bipolar depression since these receptors have increasingly attracted attention as novel pharmacotherapy targets for depression [79,80]. The ability of lurasidone to reduce immobility in animals model of depression add further support for its antidepressant actions.…”