Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion

Gurtman, Clint; Morley, Kirsten C.; Li, Kong M.; Hunt, Glenn E.; McGregor, Iain S.

doi:10.1016/s0014-2999(02)01820-4

Cited by 95 publications

(109 citation statements)

References 35 publications

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“…This is consistent with our previous results using identical treatment regimes (Gurtman et al, 2002;McGregor et al, 2003b;Morley et al, 2001).…”

Section: Acute Drug Effectssupporting

confidence: 94%

“…( 7 )3,4-Methylenedioxymethamphetamine hydrochloride was supplied by the Australian Government Analytical Laboratories (Pymble, NSW), and was diluted in 0.9% saline. Acute administration of MDMA involved procedures reported previously (Gurtman et al, 2002;McGregor et al, 2003a, b;Morley et al, 2001). Rats received a 5 mg/kg i.p.…”

Section: Methodsmentioning

confidence: 99%

“…injection of MDMA (n ¼ 26) or saline (n ¼ 25) every hour for 4 h on 2 consecutive days, giving a cumulative dose of 40 mg/kg. This dose regime of MDMA produces long-term behavioral and neurochemical effects (Gurtman et al, 2002;McGregor et al, 2003a, b;Morley et al, 2001).…”

Section: Methodsmentioning

confidence: 99%

“…This procedure provides a rapid reading of body temperature and has been used previously with minimal stress compared to other procedures (Gurtman et al, 2002;McGregor et al, 2003b;Morley et al, 2001). Following the 4 h drug administration period, all rats were housed individually in the colony overnight and replaced back in their home cages the following morning.…”

Section: Methodsmentioning

confidence: 99%

“…In recent work, we have discovered a 'MDMA syndrome' in rats given brief exposure to the drug. When tested weeks or months following brief exposure to MDMA, rats show decreased social interaction, increased anxiety on the elevated plus maze and emergence tests, poorer memory in the object recognition test and depressive-like symptoms in the forced swim test (Gurtman et al, 2002;McGregor et al, 2003a, b;Morley et al, 2001). These behavioral changes are associated with changes in the regional density of the serotonin transporter (SERT), 5-HT 2A/2C , and 5-HT 1B receptors (McGregor et al, 2003a) and, to a certain extent, changes in tissue levels of 5-HT and its metabolite 5-HIAA (Gurtman et al, 2002;McGregor et al, 2003a, b).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Thompson

Clemens

et al. 2003

Neuropsychopharmacol

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Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 Â 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

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“…This is consistent with our previous results using identical treatment regimes (Gurtman et al, 2002;McGregor et al, 2003b;Morley et al, 2001).…”

Section: Acute Drug Effectssupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Thompson

Clemens

et al. 2003

Neuropsychopharmacol

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Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats

Saadati

Sadegzadeh

Sakhaie

et al. 2021

Intl J of Devlp Neuroscience

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A survey of the literature indicates that the developmental disruptions in serotonin (5‐HT) levels can influence the brain development and the function. To the best of our knowledge, so far, there are a few studies about the effects of developmental period 5‐HT depletion on cognition and behavior of adult male and female rats. Therefore, in the present study, we examined the effects of postnatal days (PND 10–20) administration of para‐chlorophenylalanine (PCPA, 100 mg/kg, s.c) a 5‐HT synthesis inhibitor, on anxiety‐related behaviors, pain sensitivity, short‐term recognition memory, and hippocampal and prefrontal cortex (PFC) brain‐derived neurotrophic factor (BDNF) mRNA expression in adult male and female rats. Novel object recognition memory (NORM) and behavioral parameters (anxiety‐like behaviors and pain sensitivity) were evaluated in early adulthood and after that, the hippocampi and PFC of the rat's brain were removed for the determination of BDNF mRNA expression. Our results indicated that the postnatal period administration of PCPA impaired short‐term NORM. The postnatal developmental period treatment with PCPA also increased anxiety‐like behaviors in the open field and elevated plus maze (EPM) tests. Postnatal PCPA treatment increased pain sensitivity in the hot plate test in both male and female rats, especially in female animals. In addition, postnatal days serotonin depletion decreased BDNF level in the hippocampus and PFC of both male and female rats. These findings demonstrate that serotonin plays the main role in neurodevelopment, cognitive functions, and behavior. Therefore, serotonergic system dysregulation during the developmental periods may have more adverse influences on the brain development of rats.

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On the anxiogenic and anxiolytic nature of long-term cerebral 5-HT depletion following MDMA

Green

McGregor

2002

Psychopharmacology

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Increased anxiety in rats after 3,4-methylenedioxymethamphetamine: association with serotonin depletion

Cited by 95 publications

References 35 publications

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Chronic Fluoxetine Treatment Partly Attenuates the Long-Term Anxiety and Depressive Symptoms Induced by MDMA (‘Ecstasy’) in Rats

Serotonin depletion during the postnatal developmental period causes behavioral and cognitive alterations and decreases BDNF level in the brain of rats

On the anxiogenic and anxiolytic nature of long-term cerebral 5-HT depletion following MDMA

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