Abstract
Depression remains a challenge in the field of affective neuroscience, despite a steady research progress. Six out of nine basic antidepressant mechanisms rely on serotonin neurotransmitter system. Preclinical studies have demonstrated the significance of serotonin receptors (5-HT1-3,6,7), its signal transduction pathways and classical down stream targets (including neurotrophins, neurokinins, other peptides and their receptors) in antidepressant drug action. Serotonergic control of depression embraces the recent molecular requirements such as influence on proliferation, neurogenesis, plasticity, synaptic (re)modeling and transmission in the central nervous system. The present progress report analyses the credibility of each protein as therapeutically relevant target of depression. In vivo interaction studies and knockout models which identified these targets are foreseen to unearth new ligands and help them transform to drug candidates. The importance of the antidepressant assay selection at the preclinical level using salient animal models/assay systems is discussed. Such test batteries would definitely provide antidepressants with faster onset, efficacy in resistant (and co-morbid) types and with least adverse effects. Apart from the selective ligands, only those molecules which bring an overall harmony, by virtue of their affinities to various receptor subtypes, could qualify as effective antidepressants. Synchronised modulation of various serotonergic sub-pathways is the basis for a unique and balanced antidepressant profile, as that of fluoxetine (most exploited antidepressant) and such a profile may be considered as a template for the upcoming antidepressants. In conclusion, 5-HT based multi-targeted antidepressant drug discovery supported by in vivo interaction studies and knockout models is advocated as a strategy to provide classic molecules for clinical trials.
Highlights
Depression remains a challenge in the field of affective neuroscience, despite a steady research progress
The preclinical studies which attempted to clarify the role of serotonergic receptors, the secondary functional proteins and various other factors involved in control of depression are discussed
As far as the REM sleep studies are concerned, the antidepressant-like effects of 5HT7 receptor antagonists are accepted with some degree of uncertainty since the sleep pattern observed in rats and mice is in contrary to what has been observed in clinical depression. 5-HT7 receptor is involved in shaping of neuronal cytoarchitecture, especially the hippocampus and the antidepressant-like behavioural effects due to 5-HT7 antagonism can be possibly associated with altered morphology and neurogenesis [223]
Summary
Vation/suppression, protein expression, neuronal plasticity, and neurogenesis and various other inter-linked complex phenomenon associated with behavioural and neurochemical states of depression. This review updates the identified and probable neuronal targets of depression mainly pertaining to the 5-HT neurotransmitter system and attempts to highlight the significance of knockout models and interaction studies in both identifying new targets and screening specific ligands (acting directly/indirectly on the serotonergic system) for antidepressant prospects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
