Journal article
Sex-Dependent Modulation of Anxiety and Fear by 5-HT1A Receptors in the Bed Nucleus of the Stria Terminalis
ACS chemical neuroscience, Vol.10(7), pp.3154-3166
07/17/2019
DOI: 10.1021/acschemneuro.8b00594
PMCID: PMC6996028
PMID: 31140276
Abstract
Serotonin (5-hydroxytryptamine; 5-HT) coordinates behavioral responses to stress through a variety of presynaptic and postsynaptic receptors distributed across functionally diverse neuronal networks in the central nervous system. Efferent 5-HT projections from the dorsal raphe nucleus (DRN) to the bed nucleus of the stria terminalis (BNST) are generally thought to enhance anxiety and aversive learning by activating 5-HT2C receptor (5-HT2CR) signaling in the BNST, although an opposing role for postsynaptic 5-HT1A receptors has recently been suggested. In the present study, we sought to delineate a role for postsynaptic 5-HT1A receptors in the BNST in aversive behaviors using a conditional knockdown of the 5-HT1A receptor. Both males and females were tested to dissect out sex-specific effects. We found that male mice have significantly reduced fear memory recall relative to female mice and inactivation of 5-HT1A receptor in the BNST increases contextual fear conditioning in male mice so that they resemble the females. This coincided with an increase in neuronal excitability in males, suggesting that 5-HT1A receptor deletion may enhance contextual fear recall by disinhibiting fear memory circuits in the BNST. Interestingly, 5-HT1A receptor knockdown did not significantly alter anxiety-like behavior in male or female mice, which is in agreement with previous findings that anxiety and fear are modulated by dissociable circuits in the BNST. Overall, these results suggest that BNST 5-HT1A receptors do not significantly alter behavior under basal conditions, but can act as a molecular brake that buffer against excessive activation of aversive circuits in more threatening contexts.
Details
- Title: Subtitle
- Sex-Dependent Modulation of Anxiety and Fear by 5-HT1A Receptors in the Bed Nucleus of the Stria Terminalis
- Creators
- Catherine A Marcinkiewcz - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United States, Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United StatesGabrielle Bierlein-De La Rosa - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United StatesCayce E Dorrier - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United StatesMackenzie McKnight - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, United StatesJeffrey F DiBerto - Curriculum in Neurobiology, School of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United StatesDipanwati Pati - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United StatesCarol A Gianessi - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United StatesOlivia J Hon - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States, Curriculum in Neurobiology, School of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United StatesGreg Tipton - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United StatesZoe A McElligott - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States, Curriculum in Neurobiology, School of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United StatesEric Delpire - Department of Anesthesiology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, United StatesThomas L Kash - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States, Curriculum in Neurobiology, School of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, United States, Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Resource Type
- Journal article
- Publication Details
- ACS chemical neuroscience, Vol.10(7), pp.3154-3166
- DOI
- 10.1021/acschemneuro.8b00594
- PMID
- 31140276
- PMCID
- PMC6996028
- NLM abbreviation
- ACS Chem Neurosci
- ISSN
- 1948-7193
- eISSN
- 1948-7193
- Grant note
- DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: K99A024215; DOI: 10.13039/100000027, name: National Institute on Alcohol Abuse and Alcoholism, award: R01AA019454
- Language
- English
- Date published
- 07/17/2019
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984070996802771
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