Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis in SHR and WKY rats

Durand, M.; Berton, Olivier; Aguerre, Sylvie; Edno, L.; Combourieu, I.; Mormède, Pierre; Chaouloff, Francis

doi:10.1016/s0028-3908(99)00009-x

Cited by 124 publications

(82 citation statements)

References 61 publications

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“…This effect of fluoxetine mirrors previous reports (Caccia et al, 1992a(Caccia et al, , 1992bDurand et al, 1999;Hrdina, 1987) and likely reflects decreased reuptake of 5-HT in fluoxetinetreated rats, preventing metabolism of 5-HT to 5-HIAA by intraneuronal monoamine oxidase A. Chronic fluoxetine treatment also caused a modest yet significant reduction in 5-HT in the hippocampus, as has been previously noted (Caccia et al, 1992b).…”

Section: Neurochemical Resultssupporting

confidence: 88%

“…Serum levels of fluoxetine and norfluoxetine were comparable to those seen in previous studies, where the drug has been injected or gavaged into rats (Caccia et al, 1990;Durand et al, 1999). For example, Durand et al (1999) injected 10 mg/kg fluoxetine once a day for 3 weeks, and after a 30 h washout reported plasma levels of 314 ng/ml norfluoxetine, similar to the 1209 nmol/l (equivalent to 409 ng/ml) reported here.…”

Section: Acute Drug Effectssupporting

confidence: 87%

“…For example, Durand et al (1999) injected 10 mg/kg fluoxetine once a day for 3 weeks, and after a 30 h washout reported plasma levels of 314 ng/ml norfluoxetine, similar to the 1209 nmol/l (equivalent to 409 ng/ml) reported here. Caccia et al (1990) noted fluoxetine levels of approximately 300 nmol/l and norfluoxetine levels of 500 nmol/l at 6 h following oral administration of a single 10 mg/kg dose of fluoxetine to rats.…”

Section: Acute Drug Effectssupporting

confidence: 82%

“…Alternatively, reduced fluid intake may have resulted from a conditioned taste aversion produced by fluoxetine (Prendergast et al, 1996). Fluoxetine-treated rats also gained significantly less weight than controls, an effect that is consistent with other animal Caccia et al, 1997;Durand et al, 1999) and human studies (Wong et al, 1995).…”

Section: Acute Drug Effectssupporting

confidence: 73%

“…A target dose of 7 mg/kg/day fluoxetine was chosen on the basis of effective doses for modifying behavior with chronic administration in previous studies Contreras et al, 2001;Durand et al, 1999;File et al, 1999;Griebel et al, 1999;Jones et al, 2002;Silva and Brandao, 2000;. Estimating that a 500 g rat would drink approximately 20 ml of fluoxetine solution per day, the drug was dissolved in tap water at a concentration of 0.175 mg/ml, to approach the target dose of 7 mg/kg/day.…”

Section: Methodsmentioning

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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Section: Neurochemical Resultssupporting

confidence: 88%

Section: Acute Drug Effectssupporting

confidence: 87%

Section: Acute Drug Effectssupporting

confidence: 82%

Section: Acute Drug Effectssupporting

confidence: 73%

Section: Methodsmentioning

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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Brain and Cardiovascular Diseases: Molecular Aspects

Szczepañska‐Sadowska¹

2013

Metabolic Syndrome and Neurological Disorders

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Preclinical animal anxiety research – flaws and prejudices

Ennaceur

Chazot

2016

Pharmacology Res & Perspec

101

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The current tests of anxiety in mice and rats used in preclinical research include the elevated plus‐maze (EPM) or zero‐maze (EZM), the light/dark box (LDB), and the open‐field (OF). They are currently very popular, and despite their poor achievements, they continue to exert considerable constraints on the development of novel approaches. Hence, a novel anxiety test needs to be compared with these traditional tests, and assessed against various factors that were identified as a source of their inconsistent and contradictory results. These constraints are very costly, and they are in most cases useless as they originate from flawed methodologies. In the present report, we argue that the EPM or EZM, LDB, and OF do not provide unequivocal measures of anxiety; that there is no evidence of motivation conflict involved in these tests. They can be considered at best, tests of natural preference for unlit and/or enclosed spaces. We also argued that pharmacological validation of a behavioral test is an inappropriate approach; it stems from the confusion of animal models of human behavior with animal models of pathophysiology. A behavioral test is developed to detect not to produce symptoms, and a drug is used to validate an identified physiological target. In order to overcome the major methodological flaws in animal anxiety studies, we proposed an open space anxiety test, a 3D maze, which is described here with highlights of its various advantages over to the traditional tests.

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Effects of repeated fluoxetine on anxiety-related behaviours, central serotonergic systems, and the corticotropic axis in SHR and WKY rats

Cited by 124 publications

References 61 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

Brain and Cardiovascular Diseases: Molecular Aspects

Preclinical animal anxiety research – flaws and prejudices

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