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    
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.
Yann S Mineur; Emily B Einstein; Matthew P Bentham; Mattis B Wigestrand; Sam Blakeman; Sylvia A Newbold; Marina R Picciotto
Related Documents :
23083095 - Pharmacological characterization of lps and opioid interactions at the toll-like recept...
23299095 - Attenuation of cocaine and heroin seeking by μ-opioid receptor antagonism.
2850625 - Human brain receptor autoradiography using whole hemisphere sections: a general method ...
23548325 - Synergistic analgesic effects between neuronostatin and morphine at the supraspinal level.
1377715 - Co-localization of tyrosine hydroxylase, gaba and neuropeptide y within axon terminals ...
1679215 - Nmda receptors participate differentially in two different synaptic inputs in neurons o...
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:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Using Cluster Analysis to Identify Phenotypes and Validation of Mortality in Men with COPD.
Next Document:  Group-Based Differences in Anti-Aging Bias Among Medical Students.