Effect of Subchronic Antidepressant Treatments on Behavioral, Neurochemical, and Endocrine Changes in the Forced-Swim Test

Connor, Thomas J.; Kelliher, Padraig; Yan, Shi; Harkin, Andrew; Kelly, John; Leonard, Brian E.

doi:10.1016/s0091-3057(99)00192-6

Cited by 81 publications

(51 citation statements)

References 43 publications

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“…depressed or not depressed / stressed or unstressed. The rats subjected to acute, sub-chronic and chronic FST exhibit long immobility time, the magnitudes of which are similar to those exhibited by stressed animals [18,19] , hence refl ecting a depressed state. This also implies that the maximal stress is induced on the first day of FST and does not increase upon repetitive exposure.…”

Section: Discussionmentioning

confidence: 81%

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

et al. 2011

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Objective The current study was aimed to investigate the correlations between immobility time in the forced swimming test (FST, a behavioral indicator of stress level) and hippocampal monoamine levels (markers of depression), plasma adrenalin level (a peripheral marker of stress) as well as fl uoro-jade C staining (a marker of neurodegeneration).Methods Male Sprague-Dawley rats were subjected to acute, sub-chronic (7 d) or chronic (14 d) FSTs and immobility time was recorded. Levels of noradrenalin, serotonin and dopamine in the hippocampus, and adrenalin level in the plasma were quantified by high-performance liquid chromatography with electrochemical detection. Brain sections from rats after chronic forced swimming or rotenone treatment (3 mg/kg subcutaneously for 4 d) were stained with fl uoro-jade C. ResultsThe rats subjected to swimming stress (acute, sub-chronic and chronic) showed long immobility times [(214 ± 5), (220 ± 4) and (231 ± 7) s, respectively], indicating that the animals were under stress. However, the rats did not exhibit significant declines in hippocampal monoamine levels, and the plasma adrenalin level was not significantly increased compared to that in unstressed rats. The rats that underwent chronic swimming stress did not manifest fl uoro-jade C staining in brain sections, while degenerating neurons were evident after rotenone treatment. Conclusion The immobility time in the FST does not correlate with markers of depression (monoamine levels) and internal stress (adrenalin levels and neurodegeneration), hence this parameter may not be a true indicator of stress level.

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Section: Discussionmentioning

confidence: 81%

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

et al. 2011

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“…The brains were then fixed in paraformaldehyde overnight and stored in phosphate-buffered saline until sectioned for immunohistochemical analysis. These time points were based on previous studies in which the peak corticosterone secretion and expression of c-fos following exposure to the swim stress were determined (Connor et al, 2000;Duncan et al, 1996). Animals that were not exposed to swim stress were given injections, bled, and perfused at comparable time points to assess any effects of these treatments on basal activity of the HPA axis.…”

Section: Treatment Proceduresmentioning

confidence: 99%

“…Animals that were not exposed to swim stress were given injections, bled, and perfused at comparable time points to assess any effects of these treatments on basal activity of the HPA axis. This paradigm was chosen because, in rats, chronic administration of antidepressants is required to elicit the suppression of corticosterone and reduction in c-fos expression in the PVN (Connor et al, 1998(Connor et al, , 2000Duncan et al, 1996).…”

Section: Treatment Proceduresmentioning

confidence: 99%

“…Furthermore, the ability of glucocorticoid hormones to exert negative feedback on HPA axis activity appears to be deficient in depression, resulting in a feed-forward hyperactivation of this system (Parker et al, 2003;Holsboer, 2000). This enhanced output of the HPA axis appears functionally relevant to depression, as long-term antidepressant treatment attenuates this phenomenon in humans (De Bellis et al, 1993;Pariante et al, 2004;Greden et al, 1983;Michelson et al, 1997), and suppresses stress-induced activation of the HPA axis in other species (Reul et al, 1993;Connor et al, 2000;Holsboer and Barden, 1996;de Medeiros et al, 2005;Butterweck et al, 2001;Stout et al, 2002). The ability of antidepressants to suppress HPA axis hyperactivity has been shown to be coupled to their clinical efficacy (Appelhof et al, 2006;Young et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

Hill

Sinopoli

et al. 2006

Neuropsychopharmacol

109

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The efficacy of antidepressants has been linked in part to their ability to reduce activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, the mechanism by which antidepressants regulate the HPA axis is largely unknown. Given that recent research has demonstrated that endocannabinoids can regulate the HPA axis and exhibit antidepressant potential, we examined the hypothesis that the endocannabinoid system is regulated by long-term antidepressant treatment. Three-week administration of the tricyclic antidepressant desipramine (10 mg/kg/day) resulted in a significant increase in the density of the cannabinoid CB 1 receptor in the hippocampus and hypothalamus, without significantly altering endocannabinoid content in any brain structure examined. Furthermore, chronic desipramine treatment resulted in a reduction in both secretion of corticosterone and the induction of the immediate early gene c-fos in the medial dorsal parvocellular region of the paraventricular nucleus of the hypothalamus (PVN) following a 5 min exposure to swim stress. Acute treatment with the CB 1 receptor antagonist, AM251 (1 mg/kg), before exposure to swim stress, completely occluded the ability of desipramine to reduce both corticosterone secretion and induction of c-fos expression in the PVN. Collectively, these data demonstrate that CB 1 receptor density in the hippocampus and hypothalamus is increased by chronic tricyclic antidepressant treatment, and suggest that this upregulation could contribute to the ability of tricyclic antidepressants to suppress stress-induced activation of the HPA axis.

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“…Antidepressant effects in intact animals with fluoxetine have been frequently reported in the Sprague-Dawley strain (Detke et al, 1997;Detke and Lucki, 1996;Page et al, 1999), but infrequently, if ever, with Wistar strain rats. However, there is also at least one reported failure of chronic SSRIs to affect forced swim behavior in Sprague-Dawley rats at doses that clearly affected 5-HT turnover (Connor et al, 2000), suggesting that procedural factors in forced swim testing may also be important.…”

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

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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Effect of Subchronic Antidepressant Treatments on Behavioral, Neurochemical, and Endocrine Changes in the Forced-Swim Test

Cited by 81 publications

References 43 publications

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

Forced swimming stress does not affect monoamine levels and neurodegeneration in rats

Involvement of the Endocannabinoid System in the Ability of Long-Term Tricyclic Antidepressant Treatment to Suppress Stress-Induced Activation of the Hypothalamic–Pituitary–Adrenal Axis

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

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