Lithium treatment restores clonidine's effect in an animal model of depression

Aulakh, Charanjit S.; Hill, James L.; Murphy, Dennis L.

doi:10.1016/0091-3057(94)90308-5

Cited by 5 publications

(1 citation statement)

References 17 publications

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“…stress induced anhedonia [216],olfactory bulbectomy induced passive avoidance, operant tasks, and electroencephalographic studies [141, 193], and in FST [60]. In Fawn-Hooded rats short-term lithium treatment enhances 5-HT concentrations at postsynaptic 5-HT 2C receptor sites [12]. Amidst the various mechanisms behind the antidepressant effect fluoxetine, a competitive and reversible antagonism at 5-HT 2C receptor was reported [48, 229] .…”

Section: -Ht2c Receptor (Previously 5-ht1c Receptor)mentioning

confidence: 99%

Assessing the Neuronal Serotonergic Target-based Antidepressant Stratagem: Impact of In Vivo Interaction Studies and Knockout Models

Rajkumar

Mahesh²

2008

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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.

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