Considerations of Pool Dimensions in the Forced Swim Test in Predicting the Potential Antidepressant Activity of Drugs

Rosas-Sánchez, Gilberto Uriel; Germán-Ponciano, León Jesús; Rodríguez‐Landa, Juan Francisco

doi:10.3389/fnbeh.2021.757348

Cited by 8 publications

(10 citation statements)

References 72 publications

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“…Prior to the behavioral testing of VGLUT3 cKO 5‑HT mice, we first confirmed that pretreatment of wildtype mice with fluoxetine increased time spent climbing when exposed to swim stress (Mann–Whitney U = 6, p = 0.016; Supporting Information Figure 1). This result is in line with previous evidence that the climbing response to swim stress in mice is 5-HT-sensitive, unlike in rats where it is reported that the climbing response is also noradrenaline-dependent. , Perhaps surprisingly, fluoxetine had no effect on time spent immobile (Mann–Whitney U = 15, p = 0.259; Supporting Information Figure 1), but this has also been observed previously. , Although antidepressants normally reduce immobility in this paradigm, the C57BL/6 strain used here is generally less sensitive in this regard. , Moreover, the small swimming chamber dimensions used here are reported to make it difficult to detect changes in immobility behavior. , …”

Section: Resultssupporting

confidence: 93%

“…45,46 Moreover, the small swimming chamber dimensions used here are reported to make it difficult to detect changes in immobility behavior. 47,48 Interestingly, in parallel with the effects of fluoxetine, when exposed to swim stress, VGLUT3 cKO 5-HT mice also spent more time climbing versus littermate controls (Mann− Whitney U = 77, p = 0.042; Figure 6D) without having altered immobility time (Mann−Whitney U = 131.5, p = 0.917; Figure 6D). Breakdown of the climbing data into smaller time bins (2 min) suggested that the VGLUT3 cKO 5-HT mice showed persistent climbing over the duration of the experiment, rather than a higher level of climbing compared to their controls (Supporting Information Figure 6).…”

Section: Swim Stress Increased C-fos Expression In Drn Neuronsmentioning

confidence: 89%

See 1 more Smart Citation

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Gullino,

Fuller,

Dunn

et al. 2024

ACS Chem. Neurosci.

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A major subpopulation of midbrain 5-hydroxytryptamine (5-HT) neurons expresses the vesicular glutamate transporter 3 (VGLUT3) and co-releases 5-HT and glutamate, but the function of this co-release is unclear. Given the strong links between 5-HT and uncontrollable stress, we used a combination of c-Fos immunohistochemistry and conditional gene knockout mice to test the hypothesis that glutamate co-releasing 5-HT neurons are activated by stress and involved in stress coping. Acute, uncontrollable swim stress increased c-Fos immunoreactivity in neurons co-expressing VGLUT3 and the 5-HT marker tryptophan hydroxylase 2 (TPH2) in the dorsal raphe nucleus (DRN). This effect was localized in the ventral DRN subregion and prevented by the antidepressant fluoxetine. In contrast, a more controllable stressor, acute social defeat, had no effect on c-Fos immunoreactivity in VGLUT3-TPH2 co-expressing neurons in the DRN. To test whether activation of glutamate co-releasing 5-HT neurons was causally linked to stress coping, mice with a specific deletion of VGLUT3 in 5-HT neurons were exposed to acute swim stress. Compared to wildtype controls, the mutant mice showed increased climbing behavior, a measure of active coping. Wildtype mice also showed increased climbing when administered fluoxetine, revealing an interesting parallel between the behavioral effects of genetic loss of VGLUT3 in 5-HT neurons and 5-HT reuptake inhibition. We conclude that 5-HT-glutamate co-releasing neurons are recruited by exposure to uncontrollable stress. Furthermore, natural variation in the balance of 5-HT and glutamate co-released at the 5-HT synapse may impact stress susceptibility.

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Section: Resultssupporting

confidence: 93%

Section: Swim Stress Increased C-fos Expression In Drn Neuronsmentioning

confidence: 89%

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Gullino,

Fuller,

Dunn

et al. 2024

ACS Chem. Neurosci.

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“…To further confirm, we studied the antidepressant-like effects of the 18βGA using the FST, a trustworthy animal model with excellent concurrent accuracy. In the FST, rodents exposed to CUMS displayed behaviors indicative of hopelessness, and our study’s findings align with prior research [ 59 , 63 ]. 18βGA (20 and 50 mg/kg for seven days) or FXT (7 days) declined time spent immobile in the forced swim test considerably, demonstrating the antidepressant influence of 18βGA.…”

Section: Discussionsupporting

confidence: 91%

“…FST is used to detect the severity of despair in animals, and the procedure is based on past research [ 59 , 60 ]. Animals (n = 6) were trained for the first 15 min before the actual test in a cylinder tank (50 × 20 cm) with water (25 ± 2 °C, 30 cm deep).…”

Section: Methodsmentioning

confidence: 99%

18β-Glycyrrhetinic Acid Ameliorates Neuroinflammation Linked Depressive Behavior Instigated by Chronic Unpredictable Mild Stress via Triggering BDNF/TrkB Signaling Pathway in Rats

Gupta

Sharma

2022

Neurochem Res

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Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50 mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein’s expression. 18βGA (20 and 50 mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGA dramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50 mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11064-022-03779-7.

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“…1), but this has also been observed previously 42,44 . Although antidepressants normally reduce immobility in this paradigm, the C57BL/6 strain used here is generally less sensitive in this regard 45,46 Moreover, the current small swimming chamber dimensions are reported to make it difficult to detect changes in immobility behaviour 47,48 .…”

Section: Ventralmentioning

confidence: 91%

Evidence for a role of 5-HT-glutamate co-releasing neurons in acute stress mechanisms

Gullino,

Fuller,

Dunn

et al. 2023

Preprint

View full text Add to dashboard Cite

The majority of midbrain 5-hydroxytryptamine (5-HT) neurons express the vesicular glutamate transporter 3 (VGLUT3) and co-release 5-HT and glutamate, but the function of this co-release is unclear. Given the strong links between 5-HT and uncontrollable stress, we used a combination of c-Fos immunocytochemistry and conditional gene knock out in mice to test the hypothesis that glutamate co-releasing 5-HT neurons would be activated by stress and involved in stress coping.Acute, uncontrollable swim stress increased c-Fos immunoreactivity in neurons co-expressing VGLUT3 and the 5-HT marker tryptophan hydroxylase 2 (TPH2) in the dorsal raphe nucleus (DRN). This effect was localised in the ventral DRN subregion and prevented by the antidepressant fluoxetine. In contrast, a more controllable stressor, acute social defeat, had no effect on c-Fos immunoreactivity in VGLUT3-TPH2 co-expressing neurons in the DRN.To test whether activation of glutamate co-releasing 5-HT neurons was causally linked to stress coping, mice with a specific deletion of VGLUT3 in 5-HT neurons were exposed to acute swim stress. Compared to wildtype controls, the mutant mice showed increased climbing behaviour, a measure of active coping. Wildtype mice also showed increased climbing when administered fluoxetine, revealing an interesting parallel between the behavioural effects of genetic loss of VGLUT3 in 5-HT neurons and 5-HT reuptake inhibition.We conclude that 5-HT-glutamate co-releasing neurons are recruited by exposure to uncontrollable stress. Furthermore, natural variation in the balance of 5-HT and glutamate released at the 5-HT synapse may impact on stress susceptibility.

show abstract

Considerations of Pool Dimensions in the Forced Swim Test in Predicting the Potential Antidepressant Activity of Drugs

Cited by 8 publications

References 72 publications

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

Evidence for a Role of 5-HT-glutamate Co-releasing Neurons in Acute Stress Mechanisms

18β-Glycyrrhetinic Acid Ameliorates Neuroinflammation Linked Depressive Behavior Instigated by Chronic Unpredictable Mild Stress via Triggering BDNF/TrkB Signaling Pathway in Rats

Evidence for a role of 5-HT-glutamate co-releasing neurons in acute stress mechanisms

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