Document Detail


Expression of the 5-HT1A Serotonin Receptor in the Hippocampus is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine.
MedLine Citation:
PMID:  25288485     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Nicotinic acetylcholine receptor (nAChR) blockers potentiate the effects of selective serotonin reuptake inhibitors (SSRIs) in some treatment resistant patients; however, it is not known whether these effects are independent, or whether the two neurotransmitter systems act synergistically. We first determined that the SSRI fluoxetine and the nicotinic partial agonist cytisine have synergistic effects in a mouse model of antidepressant efficacy, whereas serotonin depletion blocked the effects of cytisine. Using a pharmacological approach, we found that the 5-HT1A agonist 8-OH-DPAT also potentiated cytisine's antidepressant-like effects, suggesting that this subtype might mediate the interaction between the serotonergic and cholinergic systems. 5-HT1A receptors are located both pre-synaptically and post-synaptically. We therefore knocked down 5-HT1A receptors in either the dorsal raphe (presynaptic autoreceptors) or the hippocampus (a brain area with high expression of 5-HT1A heteroreceptors sensitive to cholinergic effects on affective behaviors). Knockdown of 5-HT1A receptors in hippocampus, but not dorsal raphe, significantly decreased the antidepressant-like effect of cytisine. This study suggests that serotonin signaling through postsynaptic 5-HT1A receptors in the hippocampus is critical for the antidepressant-like effects of a cholinergic drug and begins to elucidate the molecular mechanisms underlying interactions between the serotonergic and cholinergic systems related to mood disorders.Neuropsychopharmacology accepted article preview online, 7 October 2014. doi:10.1038/npp.2014.269.
Authors:
Yann S Mineur; Emily B Einstein; Matthew P Bentham; Mattis B Wigestrand; Sam Blakeman; Sylvia A Newbold; Marina R Picciotto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-07
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  -     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-7     Completed Date:  -     Revised Date:  2014-10-8    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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