Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion

Rómeó D. Andó, C. Ádori, Eszter Kirilly, Eszter Molnár, Gábor G. Kovács, Linda Ferrington, Paul A T Kelly, G. Bagdy

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To assess the functional state of the serotonergic system, the acute behavioural and brain metabolic effect of SSRI antidepressants were studied during the recovery period after MDMA-induced neuronal damage. The effects of the SSRI fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m-CPP) were investigated in the social interaction test in Dark Agouti rats, 6 months after treatment with a single dose of MDMA (15 or 30 mg kg-1, i.p.). At earlier time points these doses of MDMA have been shown to cause 30-60% loss in axonal densities in several brain regions. Densities of the serotonergic axons were assessed using serotonin-transporter and tryptophan-hydroxylase immunohistochemistry. In a parallel group of animals, brain function was examined following an acute challenge with either fluoxetine or citalopram, using 2-deoxyglucose autoradiographic imaging. Six months after MDMA treatment the densities of serotonergic axons were decreased in only a few brain areas including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were attenuated in animals pretreated with MDMA. The metabolic response to both citalopram and fluoxetine was normal in most of the brain areas examined with the exception of ventromedial thalamus and hippocampal sub-fields where the response was attenuated. These data provide evidence that 6 months after MDMA-induced damage serotonergic axons show recovery in most brain areas, but serotonergic functions to challenges with SSRIs including anxiety and aggression remain altered.

Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalBehavioural Brain Research
Volume207
Issue number2
DOIs
Publication statusPublished - Mar 5 2010

Fingerprint

N-Methyl-3,4-methylenedioxyamphetamine
Fluoxetine
Brain
Axons
Citalopram
Thalamus
Anxiety
Tryptophan Hydroxylase
Serotonin Receptor Agonists
Serotonin Plasma Membrane Transport Proteins
Deoxyglucose
Interpersonal Relations
Aggression
Antidepressive Agents
Hippocampus
Immunohistochemistry
Therapeutics

Keywords

  • Anxiety
  • Functional imaging
  • LCMRglu
  • MDMA
  • Serotonin
  • Social interaction
  • SSRI antidepressant

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion. / Andó, Rómeó D.; Ádori, C.; Kirilly, Eszter; Molnár, Eszter; Kovács, Gábor G.; Ferrington, Linda; Kelly, Paul A T; Bagdy, G.

In: Behavioural Brain Research, Vol. 207, No. 2, 05.03.2010, p. 280-289.

Research output: Contribution to journalArticle

Andó, Rómeó D. ; Ádori, C. ; Kirilly, Eszter ; Molnár, Eszter ; Kovács, Gábor G. ; Ferrington, Linda ; Kelly, Paul A T ; Bagdy, G. / Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion. In: Behavioural Brain Research. 2010 ; Vol. 207, No. 2. pp. 280-289.
@article{24faf8ac098b40b7a6a65e766b217695,
title = "Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion",
abstract = "To assess the functional state of the serotonergic system, the acute behavioural and brain metabolic effect of SSRI antidepressants were studied during the recovery period after MDMA-induced neuronal damage. The effects of the SSRI fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m-CPP) were investigated in the social interaction test in Dark Agouti rats, 6 months after treatment with a single dose of MDMA (15 or 30 mg kg-1, i.p.). At earlier time points these doses of MDMA have been shown to cause 30-60{\%} loss in axonal densities in several brain regions. Densities of the serotonergic axons were assessed using serotonin-transporter and tryptophan-hydroxylase immunohistochemistry. In a parallel group of animals, brain function was examined following an acute challenge with either fluoxetine or citalopram, using 2-deoxyglucose autoradiographic imaging. Six months after MDMA treatment the densities of serotonergic axons were decreased in only a few brain areas including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were attenuated in animals pretreated with MDMA. The metabolic response to both citalopram and fluoxetine was normal in most of the brain areas examined with the exception of ventromedial thalamus and hippocampal sub-fields where the response was attenuated. These data provide evidence that 6 months after MDMA-induced damage serotonergic axons show recovery in most brain areas, but serotonergic functions to challenges with SSRIs including anxiety and aggression remain altered.",
keywords = "Anxiety, Functional imaging, LCMRglu, MDMA, Serotonin, Social interaction, SSRI antidepressant",
author = "And{\'o}, {R{\'o}me{\'o} D.} and C. {\'A}dori and Eszter Kirilly and Eszter Moln{\'a}r and Kov{\'a}cs, {G{\'a}bor G.} and Linda Ferrington and Kelly, {Paul A T} and G. Bagdy",
year = "2010",
month = "3",
day = "5",
doi = "10.1016/j.bbr.2009.10.011",
language = "English",
volume = "207",
pages = "280--289",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Acute SSRI-induced anxiogenic and brain metabolic effects are attenuated 6 months after initial MDMA-induced depletion

AU - Andó, Rómeó D.

AU - Ádori, C.

AU - Kirilly, Eszter

AU - Molnár, Eszter

AU - Kovács, Gábor G.

AU - Ferrington, Linda

AU - Kelly, Paul A T

AU - Bagdy, G.

PY - 2010/3/5

Y1 - 2010/3/5

N2 - To assess the functional state of the serotonergic system, the acute behavioural and brain metabolic effect of SSRI antidepressants were studied during the recovery period after MDMA-induced neuronal damage. The effects of the SSRI fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m-CPP) were investigated in the social interaction test in Dark Agouti rats, 6 months after treatment with a single dose of MDMA (15 or 30 mg kg-1, i.p.). At earlier time points these doses of MDMA have been shown to cause 30-60% loss in axonal densities in several brain regions. Densities of the serotonergic axons were assessed using serotonin-transporter and tryptophan-hydroxylase immunohistochemistry. In a parallel group of animals, brain function was examined following an acute challenge with either fluoxetine or citalopram, using 2-deoxyglucose autoradiographic imaging. Six months after MDMA treatment the densities of serotonergic axons were decreased in only a few brain areas including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were attenuated in animals pretreated with MDMA. The metabolic response to both citalopram and fluoxetine was normal in most of the brain areas examined with the exception of ventromedial thalamus and hippocampal sub-fields where the response was attenuated. These data provide evidence that 6 months after MDMA-induced damage serotonergic axons show recovery in most brain areas, but serotonergic functions to challenges with SSRIs including anxiety and aggression remain altered.

AB - To assess the functional state of the serotonergic system, the acute behavioural and brain metabolic effect of SSRI antidepressants were studied during the recovery period after MDMA-induced neuronal damage. The effects of the SSRI fluoxetine and the serotonin receptor agonist meta-chloro-phenylpiperazine (m-CPP) were investigated in the social interaction test in Dark Agouti rats, 6 months after treatment with a single dose of MDMA (15 or 30 mg kg-1, i.p.). At earlier time points these doses of MDMA have been shown to cause 30-60% loss in axonal densities in several brain regions. Densities of the serotonergic axons were assessed using serotonin-transporter and tryptophan-hydroxylase immunohistochemistry. In a parallel group of animals, brain function was examined following an acute challenge with either fluoxetine or citalopram, using 2-deoxyglucose autoradiographic imaging. Six months after MDMA treatment the densities of serotonergic axons were decreased in only a few brain areas including hippocampus and thalamus. Basal anxiety was unaltered in MDMA-treated animals. However, the acute anxiogenic effects of fluoxetine, but not m-CPP, were attenuated in animals pretreated with MDMA. The metabolic response to both citalopram and fluoxetine was normal in most of the brain areas examined with the exception of ventromedial thalamus and hippocampal sub-fields where the response was attenuated. These data provide evidence that 6 months after MDMA-induced damage serotonergic axons show recovery in most brain areas, but serotonergic functions to challenges with SSRIs including anxiety and aggression remain altered.

KW - Anxiety

KW - Functional imaging

KW - LCMRglu

KW - MDMA

KW - Serotonin

KW - Social interaction

KW - SSRI antidepressant

UR - http://www.scopus.com/inward/record.url?scp=74449083688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74449083688&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2009.10.011

DO - 10.1016/j.bbr.2009.10.011

M3 - Article

C2 - 19840819

AN - SCOPUS:74449083688

VL - 207

SP - 280

EP - 289

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

IS - 2

ER -