Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect

In all animals, losers of a conflict against a conspecific exhibit reduced aggressiveness, often coupled with depression-like symptoms, particularly after multiple defeats. While serotonin (5HT) is involved, discovering its natural role in aggression and depression has proven elusive. We show how 5H...

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Main Authors: Jan Rillich, Paul A. Stevenson
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnbeh.2018.00233/full
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author Jan Rillich
Paul A. Stevenson
author_facet Jan Rillich
Paul A. Stevenson
author_sort Jan Rillich
collection DOAJ
description In all animals, losers of a conflict against a conspecific exhibit reduced aggressiveness, often coupled with depression-like symptoms, particularly after multiple defeats. While serotonin (5HT) is involved, discovering its natural role in aggression and depression has proven elusive. We show how 5HT influences aggression in male crickets, before, and after single and multiple defeats using serotonergic drugs, at dosages that had no obvious deleterious effect on general motility: the 5HT synthesis inhibitor alpha-methyltryptophan (AMTP), the 5HT2 receptor blocker ketanserin, methiothepin which blocks 5HT receptor subtypes other than 5HT2, 5HT's precursor 5-hydroxytryptophan (5HTP) and re-uptake inhibitor fluoxetine. Contrasting reports for other invertebrates, none of the drugs influenced aggression at the first encounter. However, the recovery of aggression after single defeat, which normally requires 3 h in crickets, was severely affected. Losers that received ketanserin or AMTP regained their aggressiveness sooner, whereas those that received fluoxetine, 5HTP, or methiothepin failed to recover within 3 h. Furthermore, compared to controls, which show long term aggressive depression 24 h after 6 defeats at 1 h intervals, crickets that received AMTP or ketanserin regained their full aggressiveness and were thus more resilient to chronic defeat stress. In contrast, 5HTP and fluoxetine treated crickets showed long term aggressive depression 24 h after only 2 defeats, and were thus more susceptible to defeat stress. We conclude that 5HT acts after social defeat via a 5HT2 like receptor to maintain depressed aggressiveness after defeat, and to promote the susceptibility to and establishment of long-term depression after chronic social defeat. It is known that the decision to flee and establishment of loser depression in crickets is controlled by nitric oxide (NO), whereas dopamine (DA), but not octopamine (OA) is necessary for recovery after defeat. Here we show that blocking NO synthesis, just like ketanserin, affords resilience to multiple defeat stress, whereas blocking DA receptors, but not OA receptors, increases susceptibility, just like fluoxetine. We discuss the possible interplay between 5HT, NO, DA, and OA in controlling aggression after defeat, as well as similarities and differences to findings in mammals and other invertebrate model systems.
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spelling doaj.art-48332d1c7662492984d7eaccedfd173c2022-12-22T03:51:04ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532018-10-011210.3389/fnbeh.2018.00233414668Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model InsectJan RillichPaul A. StevensonIn all animals, losers of a conflict against a conspecific exhibit reduced aggressiveness, often coupled with depression-like symptoms, particularly after multiple defeats. While serotonin (5HT) is involved, discovering its natural role in aggression and depression has proven elusive. We show how 5HT influences aggression in male crickets, before, and after single and multiple defeats using serotonergic drugs, at dosages that had no obvious deleterious effect on general motility: the 5HT synthesis inhibitor alpha-methyltryptophan (AMTP), the 5HT2 receptor blocker ketanserin, methiothepin which blocks 5HT receptor subtypes other than 5HT2, 5HT's precursor 5-hydroxytryptophan (5HTP) and re-uptake inhibitor fluoxetine. Contrasting reports for other invertebrates, none of the drugs influenced aggression at the first encounter. However, the recovery of aggression after single defeat, which normally requires 3 h in crickets, was severely affected. Losers that received ketanserin or AMTP regained their aggressiveness sooner, whereas those that received fluoxetine, 5HTP, or methiothepin failed to recover within 3 h. Furthermore, compared to controls, which show long term aggressive depression 24 h after 6 defeats at 1 h intervals, crickets that received AMTP or ketanserin regained their full aggressiveness and were thus more resilient to chronic defeat stress. In contrast, 5HTP and fluoxetine treated crickets showed long term aggressive depression 24 h after only 2 defeats, and were thus more susceptible to defeat stress. We conclude that 5HT acts after social defeat via a 5HT2 like receptor to maintain depressed aggressiveness after defeat, and to promote the susceptibility to and establishment of long-term depression after chronic social defeat. It is known that the decision to flee and establishment of loser depression in crickets is controlled by nitric oxide (NO), whereas dopamine (DA), but not octopamine (OA) is necessary for recovery after defeat. Here we show that blocking NO synthesis, just like ketanserin, affords resilience to multiple defeat stress, whereas blocking DA receptors, but not OA receptors, increases susceptibility, just like fluoxetine. We discuss the possible interplay between 5HT, NO, DA, and OA in controlling aggression after defeat, as well as similarities and differences to findings in mammals and other invertebrate model systems.https://www.frontiersin.org/article/10.3389/fnbeh.2018.00233/fullaggressionagonistic behaviorsubjugationloser effect5HTnitric oxide
spellingShingle Jan Rillich
Paul A. Stevenson
Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
Frontiers in Behavioral Neuroscience
aggression
agonistic behavior
subjugation
loser effect
5HT
nitric oxide
title Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
title_full Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
title_fullStr Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
title_full_unstemmed Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
title_short Serotonin Mediates Depression of Aggression After Acute and Chronic Social Defeat Stress in a Model Insect
title_sort serotonin mediates depression of aggression after acute and chronic social defeat stress in a model insect
topic aggression
agonistic behavior
subjugation
loser effect
5HT
nitric oxide
url https://www.frontiersin.org/article/10.3389/fnbeh.2018.00233/full
work_keys_str_mv AT janrillich serotoninmediatesdepressionofaggressionafteracuteandchronicsocialdefeatstressinamodelinsect
AT paulastevenson serotoninmediatesdepressionofaggressionafteracuteandchronicsocialdefeatstressinamodelinsect