Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning

Philip Johnson, Andrei Molosh, Stephanie D. Fitz, Dave Arendt, Gerald A. Deehan, Lauren M. Federici, Cristian Bernabe, Eric Engleman, Zachary Rodd, Christopher A. Lowry, Anantha Shekhar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5 days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ∼ 40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

Original languageEnglish (US)
Pages (from-to)174-179
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume138
DOIs
StatePublished - Nov 1 2015

Fingerprint

5,7-Dihydroxytryptamine
Fear
Serotonin
Anxiety
Pharmacology
Rats
Norepinephrine
Desipramine
Serotonin Agents
Freezing
Injections
Dopamine
Interpersonal Relations
Basolateral Nuclear Complex
Conditioning (Psychology)
Data storage equipment
Cues
Shock
Testing

Keywords

  • 5,7-dht
  • 5-ht
  • Amygdala
  • Anxiety
  • Dorsal raphe
  • Fear
  • Sert

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning. / Johnson, Philip; Molosh, Andrei; Fitz, Stephanie D.; Arendt, Dave; Deehan, Gerald A.; Federici, Lauren M.; Bernabe, Cristian; Engleman, Eric; Rodd, Zachary; Lowry, Christopher A.; Shekhar, Anantha.

In: Pharmacology Biochemistry and Behavior, Vol. 138, 01.11.2015, p. 174-179.

Research output: Contribution to journalArticle

Johnson, Philip ; Molosh, Andrei ; Fitz, Stephanie D. ; Arendt, Dave ; Deehan, Gerald A. ; Federici, Lauren M. ; Bernabe, Cristian ; Engleman, Eric ; Rodd, Zachary ; Lowry, Christopher A. ; Shekhar, Anantha. / Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning. In: Pharmacology Biochemistry and Behavior. 2015 ; Vol. 138. pp. 174-179.
@article{369c2c71d0014e6c90ba78581152c7b0,
title = "Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning",
abstract = "The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5 days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ∼ 40{\%} without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.",
keywords = "5,7-dht, 5-ht, Amygdala, Anxiety, Dorsal raphe, Fear, Sert",
author = "Philip Johnson and Andrei Molosh and Fitz, {Stephanie D.} and Dave Arendt and Deehan, {Gerald A.} and Federici, {Lauren M.} and Cristian Bernabe and Eric Engleman and Zachary Rodd and Lowry, {Christopher A.} and Anantha Shekhar",
year = "2015",
month = "11",
day = "1",
doi = "10.1016/j.pbb.2015.09.021",
language = "English (US)",
volume = "138",
pages = "174--179",
journal = "Pharmacology, Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning

AU - Johnson, Philip

AU - Molosh, Andrei

AU - Fitz, Stephanie D.

AU - Arendt, Dave

AU - Deehan, Gerald A.

AU - Federici, Lauren M.

AU - Bernabe, Cristian

AU - Engleman, Eric

AU - Rodd, Zachary

AU - Lowry, Christopher A.

AU - Shekhar, Anantha

PY - 2015/11/1

Y1 - 2015/11/1

N2 - The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5 days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ∼ 40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

AB - The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5 days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ∼ 40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.

KW - 5,7-dht

KW - 5-ht

KW - Amygdala

KW - Anxiety

KW - Dorsal raphe

KW - Fear

KW - Sert

UR - http://www.scopus.com/inward/record.url?scp=84944036724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944036724&partnerID=8YFLogxK

U2 - 10.1016/j.pbb.2015.09.021

DO - 10.1016/j.pbb.2015.09.021

M3 - Article

VL - 138

SP - 174

EP - 179

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

SN - 0091-3057

ER -