Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test

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.

Section: Fluoxetine and Mdma Behavioral Effectsmentioning

confidence: 41%

Section: Fluoxetine and Mdma Behavioral Effectsmentioning

confidence: 99%

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

Thompson

Clemens

et al. 2003

“…Additional experiments in which 5-HT synthesis is blocked with p-cholophenylalanine (PCPA) can be performed to test this hypothesis. Involvement of 5-HT in the increased swimming activity was demonstrated by Page et al (1999) by blocking the synthesis of 5-HT with PCPA and suppressing the effects of 5-HT antidepressant drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Quantification of behaviors was performed by recording the predominant behavior in each 5 s period (Cryan and Lucki, 2000). We validated the scoring of the forced-swim test in our laboratory by treating additional normal control rats with desipramine (20 mg/kg subcutaneous) following standard procedures (Page et al, 1999). Results were similar to those reported previously: that is, increased climbing activity (17.872.7 counts vs 6.073.8 in saline treated animals) and decreased immobility (24.072.3 vs 38.376.6 in saline animals (Page et al, 1999).…”

Section: Forced-swim Testmentioning

confidence: 99%

Total Sleep Deprivation Decreases Immobility In The Forced-Swim Test

Rodríguez

Kim

Poland

2004

Sleep deprivation can exert antidepressant effects in humans in less than 24 h, making it the fastest acting antidepressant treatment. However, it is rarely used clinically because the effect disappears once the subject goes back to sleep. An understanding of the neurobiological mechanisms underlying the antidepressant effect of sleep deprivation should help to develop new rapidly acting antidepressant strategies. In the present report, an animal model of depression (the forced-swim test) was used to determine whether the effects of total sleep deprivation parallel those obtained with antidepressant drugs. Using the disk-over-water method, rats deprived of sleep for 24 h exhibited increased swimming behavior when compared to cage control rats, mimicking the effects of serotonergic antidepressants. After 48 h, sleep-deprived rats exhibited increased swimming when compared to both cage control and stimulus control rats, demonstrating that the effect is due to sleep deprivation per se, and not to extraneous factors inherent in the sleep deprivation protocol (such as stress and movement). We believe that this paradigm can be used to study the neurobiological mechanisms of rapid antidepressant effects induced by sleep deprivation.

“…Both SSRIs tested (ie fluoxetine and paroxetine), as well as the tricyclic, desipramine, the monoamine oxidase inhibitor, tranylcypromine, and the SNRI, nefazodone, dose-dependently decreased immobility in the FST indicative of an antidepressant-like effect. It is interesting to note that several of the antidepressant compounds tested were effective at reducing immobility in the gerbil FST at much lower doses as compared to those typically reported for mice and rats (Porsolt et al, 1977a, b;1978a, b;Page et al, 1999;Karolewicz and Paul, 2001;Bianchi et al, 2002;Crowley et al, 2004), although it is difficult to make direct comparisons because of the different routes of administration used in the present study (ie oral) vs many of the other studies (eg i.p.). Overall, these data are suggestive that the gerbil may be more sensitive species to psychoactive substances compared to mice and rats.…”

Section: Discussionmentioning

confidence: 55%

Behavioral and Pharmacological Validation of the Gerbil Forced-Swim Test: Effects of Neurokinin-1 Receptor Antagonists

Wallace-Boone

Newton

Wright

et al. 2007

Several studies have suggested that neurokinin-1 (NK1) receptor antagonists may have therapeutic potential as novel antidepressant drugs. To test these compounds preclinically, gerbils have become one of the preferred species in that they demonstrate close NK1 receptor homology with humans and bind NK1 antagonists with higher affinity than rats and mice. The intent of the present study was to determine whether the forced-swim test (FST), one of the most commonly used animal tests of antidepressant-like activity, could be adapted for use with the gerbil. Critical factors in the establishment of this assay included swim tank diameter, weight, and sex of the animals tested. Pharmacological validation of the FST using standard antidepressant compounds (eg fluoxetine, paroxetine, desipramine) resulted in decreased immobility time during the test, indicative of an antidepressant-like effect. Similar to results reported for the rat and mouse FST, the antipsychotic drug haloperidol increased immobility, whereas the psychostimulant, amphetamine decreased immobility, and anxiolytic drugs (eg buspirone) had no effect. Investigation into the locomotor effects of all compounds tested was consistent with previous reports in other species, with the exception of paroxetine, which produced hyperactivity at therapeutically effective doses in gerbils. In addition to standard antidepressants, NK1 antagonists (L-733060, MK-869, and CP-122721) all reduced immobility in the gerbil FST without affecting locomotor activity. Overall, these results suggest that the gerbil is an ideal species for use in the FST, and that this paradigm may have predictive validity for identifying novel antidepressant compounds.