Tail Suspension Test In Mice Research Articles

AMPA glutamate receptors mediate the antidepressant-like effects of N-acetylcysteine in the mouse tail suspension test

The aim of this study was to investigate the involvement of noradrenaline, serotonin, and subtypes of glutamate receptors in the antidepressant-like effects of N-acetylcysteine (NAC). The tail suspension test was used with male CF1 albino mice. D,L-α-methyl-ρ-tyrosine and ρ-chlorophenylalanine methyl ester hydrochloride were used as synthesis inhibitors of noradrenaline and serotonin, respectively. N-methyl-D-aspartate (NMDA) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione were used as an NMDA receptor agonist and an α-amino acid-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptor antagonist, respectively. NAC (10, 25, and 50 mg/kg intraperitoneally) significantly (P<0.05) decreased tail suspension test immobility time, whereas pretreatment with D,L-α-methyl-ρ-tyrosine, ρ-chlorophenylalanine methyl ester hydrochloride, and NMDA partially prevented (P<0.05) the effects of NAC (25 mg/kg), and pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione completely abolished (P<0.01) this effect. The study corroborates the antidepressant-like effects of NAC in the TST, a model with a well-established predictive value. The results point to the key role of AMPA receptors in the mechanism of the antidepressant-like action of NAC. Like other AMPA potentiators, NAC indirectly modulates noradrenaline and serotonin pathways. It is suggested that the value of NAC as an antidepressant arises from combined and intertwined effects on a variety of pathways.

Zinc deficiency induces behavioral alterations in the tail suspension test in mice. Effect of antidepressants

BackgroundRecently, experimental zinc deficiency has been correlated with depression-like alterations in rodents. MethodsIn the first part of present study, the time course of zinc deficient diet induced alterations in the tail suspension test (TST) in mice was investigated. In the second part, the effect of imipramine and escitalopram in control and zinc-deprived for 3 weeks mice was examined in the TST. ResultsA 4- and 10-week administration of a Zn-deficient diet enhanced the immobility time in the TST (by 20% and 57%, respectively). By contrast, a 2-week period of a zinc deficient diet effected the reduction (by 24%) of the immobility time. Moreover, a 2- and 4-week (but not 10-week) of a Zn-deficient diet resulted in the reduction of the body weight (by 37% and 18%, respectively). These results indicate the developing response to zinc deficiency induced by a zinc-deficient diet. The antidepressant-like effect (reduction in the immobility time) of both drugs was significantly reduced in zinc-deprived mice, which suggests treatment-resistance induced by zinc deprivation. ConclusionsZinc deprivation induces “pro-depressive” behavior and alters antidepressant efficacy.

Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB‐1020: Implications for treatment of attention‐deficit hyperactivity disorder

We report on the pharmacological, behavioral, and neurochemical characterization of a novel dual norepinephrine (NE)/dopamine (DA) transporter inhibitor EB-1020 (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane HCl). EB-1020 preferentially inhibited monoamine reuptake in cloned cell lines transfected with human transporters with IC₅₀ values of 6 and 38, respectively, for NE and DA transporters. In microdialysis studies, EB-1020 markedly increased NE, and DA concentrations levels in rat prefrontal cortex in vivo with peak increases of 375 and 300%, respectively with the greatest effects on NE, and also increased DA extracellular concentrations in the striatum to 400% of baseline concentrations. Behavioral studies demonstrated that EB-1020 dose-dependently decreased immobility in the mouse tail suspension test of depression to 13% of control levels, and did not stimulate locomotor activity in adult rats in the optimal dose range. EB-1020 dose-dependently inhibited locomotor hyperactivity in juvenile rats lesioned with the neurotoxin 6-hydroxydopamine (100 μg intracisternally) as neonates; a well-established animal model for attention-deficit hyperactivity disorder (ADHD). These data suggest that EB-1020 mediates its actions by stimulating NE and DA neurotransmission, which are typically impaired in ADHD.

Identification and quantification of the major volatile constituents in antidepressant active fraction of xiaoyaosan by gas chromatography–mass spectrometry

Ethnopharmacological relevanceXiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of “Taiping Huimin Heji Jufang” in Song Dynasty (960–1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. Materials and methodsAn experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC–MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction. ResultsIn the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%. ConclusionsThe petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds.

Ferulic acid exerts antidepressant-like effect in the tail suspension test in mice: Evidence for the involvement of the serotonergic system

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phenolic compound present in several plants with claimed beneficial effects in prevention and treatment of disorders linked to oxidative stress and inflammation. In this study, we aimed to verify the possible antidepressant-like effect of acute oral administration of ferulic acid in the forced swimming test (FST) and tail suspension test (TST) in mice. Additionally, the mechanisms involved in the antidepressant-like action and the effects of the association of ferulic acid with the antidepressants fluoxetine, paroxetine, and sertraline in the TST were investigated. Ferulic acid produced an antidepressant-like effect in the FST and TST (0.01–10mg/kg, p.o.), without accompanying changes in ambulation. The pretreatment of mice with WAY100635 (0.1mg/kg, s.c., a selective 5-HT1A receptor antagonist) or ketanserin (5mg/kg, i.p., a 5-HT2A receptor antagonist) was able to reverse the anti-immobility effect of ferulic acid (0.01mg/kg, p.o.) in the TST. The combination of fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.) or sertraline (1mg/kg, p.o.) with a sub-effective dose of ferulic acid (0.001mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST, without causing hyperlocomotion in the open-field test. Taken together, these results demonstrate that ferulic acid exerts antidepressant-like effect in the FST and TST in mice through modulation of the serotonergic system.

Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice.

This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (ULEtOH) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOH in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOH exhibited antidepressant-like activity in FST and TST in mice. ULEtOH increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH. ULEtOH inhibited the activity of MAO-A. The amount of RHY in ULEtOH was 17.12 mg/g extract. Our findings support the view that ULEtOH exerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOH may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice.

Role for monoaminergic systems in the antidepressant-like effect of ethanol extracts from Hemerocallis citrina

Ethnopharmacological relevanceHemerocallis citrina, a traditional herbal medicine, has been used for the improvement of emotions in Eastern-Asia countries. Aim of the studyHerein, we explored the antidepressant-like effect and its monoaminergic mechanism of the ethanol extracts from Hemerocallis citrina (HCE). Materials and methodsEffect of HCE (90, 180 and 360mg/kg, p.o.) on the immobility time was assessed in the mouse forced swim test (FST) and tail suspension test (TST), and locomotor activity was evaluated in the open-field test (OFT). Additionally, the monoamine neurotransmitters serotonin (5-HT), noradrenaline (NA) and dopamine (DA) levels involved in the antidepressant-like effect of HCE were also measured in the mice brain regions of frontal cortex and hippocampus. ResultsHCE (90, 180 and 360mg/kg, p.o.) administration significantly reduced the immobility time in both the FST and TST without accompanying changes in locomotor activity in the OFT. The pretreatment of mice with WAY 100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), cyproheptadine (3mg/kg, i.p., a 5-HT2 receptor antagonist), prazosin (62.5μg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), propranolol (5mg/kg, i.p., a β-adrenoceptor antagonist) or sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), but not SCH23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist) prevented the antidepressant-like effect of HCE (360mg/kg, p.o.) in the TST. In addition, HCE enhanced 5-HT and NA levels in the frontal cortex and hippocampus as well as elevated DA levels in the frontal cortex. ConclusionThe results indicate that the antidepressant-like effect of HCE is dependent on the serotonergic (5-HT1A and 5-HT2 receptors), noradrenergic (α1-, α2- and β-adrenoceptors) and dopaminergic (D2 receptor) systems as well as the elevation of 5-HT, NA and DA levels in the mouse brain.

Evaluation of role of noradrenergic system in the antidepressant activity of tramadol using tail suspension test in Albino mice

Evaluation of role of noradrenergic system in the antidepressant activity of tramadol using tail suspension test in Albino mice

Synthesis and antidepressant activity of di substituted-5-aryl-1,2,4-triazoles

A series of 5-aryl-1H-1,2,4-triazole-3-thiol (3) were synthesized. Alkylation of thiol group with N,N-dimethyl/diethyl/dicyclo hexyl-(2-chloro ethyl) amine gave compounds N,N-disubstituted-2-(5-aryl-1H-1,2,4-triazol-3-ylthio)ethanamine (4). These compounds were characterized on the basis of IR, 1H NMR, Mass spectral data, and elemental analysis. The newly synthesized compounds were screened for their antidepressant activity by using tail suspension test in mice.

Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: A comparison of SSR180711 and PNU-282987

Emerging evidence points to an involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. Nicotine improves symptoms of depression in humans and shows antidepressant-like effects in rodents. Monoamine release is facilitated by nAChR stimulation, and nicotine-evoked serotonin (5-HT) release has been shown to depend on α7 nAChR activation. The α7 nAChR agonist PNU-282987 shows no antidepressant-like activity when tested alone in the mouse forced swim (mFST) or tail suspension tests (mTST). However, in combination with a sub-active dose of the selective 5-HT reuptake inhibitor citalopram, inducing ~50% 5-HT reuptake inhibition, PNU-282987 has shown marked antidepressant-like effects in the mFST. SSR180711 is a recently described α7 nAChR agonist that has shown antidepressant-like activity in the rat forced swim test. To address the possibility that 5-HT reuptake inhibition contributes to the antidepressant-like profile of SSR180711, we compared the behavioural and biochemical profiles of PNU-282987 and SSR180711. In the mFST and mTST, SSR180711 (3–30mg/kg, s.c.) showed dose-dependent antidepressant-like activity, while PNU-282987 (3–30mg/kg, s.c.) showed no significant effect. The ED50 to displace [3H]α-bungarotoxin binding was 1.7 and 5.5mg/kg for SSR180711 and PNU-282987, respectively, suggesting that both compounds produce near-maximal α7 nAChR occupancy at the highest dose. While PNU-282987 did not affect ex vivo [3H]5-HT uptake, SSR180711 inhibited [3H]5-HT uptake with an ED50 of 30mg/kg. This degree of inhibition is similar to that observed with a citalopram dose of ~2.4mg/kg, a dose that is normally not active in the mFST or mTST. This suggests that the antidepressant-like activity of SSR180711 may involve partial 5-HT reuptake inhibition. SSR180711 therefore represents a compound displaying the synergistic effect of α7 nAChR agonism combined with partial 5-HT reuptake inhibition previously described. The addition of α7 nAChR agonism to classical monoamine-based mechanisms may represent a novel option for the improved treatment of major depression.

Regulatory role of the dopamine and norepinephrine transporters in pentylenetetrazol-kindled mice: Association with effect of antidepressants

In clinical practice, patients with epilepsy are frequently associated with psychiatric disorders, including cognitive impairment, depression, and attention deficit hyperactivity disorder. In fact, patients with epilepsy often take centrally acting drugs, such as antidepressants and anxiolytics; however, it remains unclear whether epilepsy is associated with psychiatric function. The present study examined the effect of kindled epileptic seizures on depression-like behavior in mice. The immobility time of pentylenetetrazol-kindled mice was as long as the immobility time of the controls in both a forced swimming test and a tail suspension test. Bupropion (10 mg/kg, i.p.) decreased the duration of immobility in the forced swimming test of pentylenetetrazol-kindled mice, while having no significant effect in controls. Furthermore, atomoxetine (2 mg/kg, i.p.) caused a significant decrease in the duration of immobility in the tail suspension test of the pentylenetetrazol-kindled mice, while having no significant effect in controls. Using immunohistochemistry, it was shown that there was no significant change in dopamine transporter levels in the striatum; however, norepinephrine transporter was significantly increased in the perirhinal cortex of the pentylenetetrazol-kindled mice. These results suggested that bupropion (in low doses) and atomoxetine are good candidates for the treatment of patients with epilepsy who suffer from psychiatric symptoms. Furthermore, this mechanism may be involved in the change of norepinephrine transporter expression, at least in the perirhinal cortex.

English

We evaluated the anti-depressive activity of ethanolic extracts of&nbsp;Gardenia jasminoides&nbsp;Ellis. (GJ&nbsp;EtOH),&nbsp;Gardenia jasminoides&nbsp;Ellis. var.&nbsp;grandiflora&nbsp;Nakai. (GJG&nbsp;EtOH) and geniposide with mouse forced swimming test (FST) and tail suspension test (TST). In addition, we investigated the possible mechanisms of action of anti-depressive effect of geniposide (GPO). The results showed that GJEtOH&nbsp;(0.1, 1.0 g/kg, p.o.) and GJG&nbsp;EtOH&nbsp;(0.1, 1.0 g/kg, p.o.) significantly reduced the immobility time of mice in both FST and TST, but they did not affect the locomotor activity of mice. Geniposide (10 mg/kg, i.p.) augmented the anti-depressive effect of desipramine (5 mg/kg, i.p.) and fluoxetine (5 mg/kg, i.p.) in the FST, but it did not affect the anti-depressive effect of clorgyline and maprotiline. Geniposide (10 mg/kg, i.p.) increased the levels of serotonin and 5-HIAA in striatum and serotonin in hippocampus. These results suggested that anti-depressive mechanism of GPO may be related to the increasing serotonin level in striatum and hippocampus in mice. &nbsp; Key words:&nbsp;Gardenia jasminoides&nbsp;Ellis.,&nbsp;Gardenia jasminoides&nbsp;Ellis. var.&nbsp;grandiflora&nbsp;Nakai., geniposide, forced swimming test, anti-depressive effect, monoamines.

ChemInform Abstract: Neurochemical Mechanisms of a Novel Alzheimer′s Disease Therapeutics on Improvement of Cognition and Depressive Behavior

AbstractReview: 42 refs.

The novel trisubstituted pyran derivative D-142 has triple monoamine reuptake inhibitory activity and exerts potent antidepressant-like activity in rodents

Major depression disorder is a significant health problem with 10-20% of all adults suffering from this disease. The underlying causes of depression are still unclear and 15% of depressed patients are resistant to all known therapies. Monoamine therapies have so far been the most successful approach for treating depression. Triple monoamine reuptake inhibitors have recently been implicated in generation of potent antidepressant activity while possibly exhibiting a low side-effect profile in addition to treating anhedonia. The additional, previously under-appreciated involvement of dopaminergic systems in depression prompted our efforts to develop novel asymmetric trisubstituted and disubstituted pyran derivatives as triple reuptake inhibitors. One of the lead compounds, D-142, exhibited uptake inhibition (K(i)) values of 29.3 nM, 14.7 nM and 59.3 ± 13.7 nM for norepinephrine, serotonin and dopamine transporters, respectively. Its affinity for serotonin transporter was comparable to fluoxetine, a well known SSRI. In the rat forced swimming test, compound D-142 exhibited potent antidepressant activity in the dose range tested (2.5, 5 and 10mg/kg) and was far more efficacious than the reference compound imipramine. In the mouse tail suspension test, compound D-142 reduced immobility in a dose (2.5, 5 and 10mg/kg) dependent manner, indicating a potent antidepressant effect. In locomotor activity tests, compound D-142 did not exhibit any stimulation in the same dose ranges. In the extended CNS receptors screening assay this molecule exhibited little or no non-specific interaction in the CNS, indicating high specificity for monoamine transporters. These results advance D-142 as a potential potent antidepressant.

Antidepressant–like effects of Acorus calamus in forced swimming and tail suspension test in mice

Objective To evaluate the antidepressant activity of methanolic extract of rhizomes of Acorus calamus ( A. calamus). Methods Tail suspension test (TST) and forced swimming test (FST) in mice were used to evaluate the antidepressant activity of methanolic extract of rhizomes of A. calamus. Methanolic extracts (50 and 100 mg/kg i.p.) were administered daily for 7 days. Imipramine 5 mg/kg was used as standard antidepressant agent throughout the study. Results Test extracts of A. calamus decreased immobility periods significantly in a dose dependent manner in both TST and FST. The observed results were also comparable with known standard drug i.e. imipramine. The flavonoid apigenin, which selectively binds with high affinity to the central benzodiazepines receptor, possesses important anxiolytic and antidepressant activities. The review of literature reveals that the A. calamus contains saponin, glycosides, tannin and flavonoid. Conclusions Methanolic extract of A. calamus rhizomes shows antidepressant activity probably through interaction with adrenergic, dopaminergic serotonergic and γ-aminobutyric acid (GABA) nergic system. Both the models have been proved to be equally valuable for demonstration of substances with a potential antidepressant activity.

Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in mice

The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana glechomifolia extract enriched in valepotriates was investigated in a mice tail suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased mice immobility in the FST (0.5-20 mg/kg p.o.) and elicited a biphasic dose-response relationship in the TST (1-20 mg/kg p.o.) with no alterations in locomotor activity and motor coordination (assessed in the open-field and rota-rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5 mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1 mg/kg, i.p., an α2 adrenoceptor antagonist), SCH 23390 (15 μg/kg, s.c., D1 dopamine receptor antagonist) and sulpiride (50 mg/kg, i.p., D2 dopamine receptor antagonist). However, mice pre-treatments with prazosin (1 mg/kg, i.p., α1 adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4×100 mg/kg/day, i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25 mg/kg) and imipramine (10 mg/kg), desipramine (5 mg/kg) and bupropion (3 mg/kg) at sub-effective doses significantly reduced mice immobility time in the FST. These data provide the first evidence of the antidepressant-like activity of V. glechomifolia valepotriates, which is due to an interaction with dopaminergic and noradrenergic neurotransmission.

Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l-arginine–nitric oxide–cyclic guanosine monophosphate pathway

1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a novel putative trace amine receptor modulator hypothesized to be useful for treatment–resistant depression. In our previous study, we have demonstrated the antidepressant-like effect of this molecule in mouse forced swim and tail suspension tests and shown to act via modulating the levels of norepinephrine, serotonin and dopamine. The present study attempts to explore the involvement of l-arginine–nitric oxide–cyclic guanosine monophosphate pathway in the antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750 mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS) inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol (2 mg/kg, i.p.) in this test model. Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was reversed by sildenafil (5 mg/kg, i.p.), a phosphodiesterase inhibitor. In conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine–nitric oxide–cyclic guanosine monophospate signaling pathway.

P.2.d.021 Antidepressant -like effect of creatine in mice: involvement of the dopaminergic system

The present study investigated a possible antidepressant-like activity of bis selenide using two predictive tests for antidepressant effect on rodents: the forced swimming test (FST) and the tail suspension test (TST). Bis selenide (0.5–5 mg/kg, p.o.) decreased the immobility time in the mouse FST and TST. The anti-immobility effect of bis selenide (1 mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), and ondasentron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), or WAY 100635 (0.1 mg/kg, s.c., a selective 5-HT1A receptor antagonist) did not block the antidepressant-like effect of bis selenide (1 mg/kg, p.o.) in the TST. Administration of bis selenide (0.1 mg/kg, p.o.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. Bis selenide did not alter Na+ K+ ATPase, MAO-A and MAO-B activities in whole brains of mice. Bis selenide produced an antidepressant-like effect in the mouse TST and FST, which may be related to the serotonergic system (5-HT2A/2C and 5-HT3 receptors).

Assessment time affects the outcome of the tail suspension test

The mouse tail suspension test (TST) is a method to screen antidepressants. Antidepressants reduce the amount of time spent immobile during the TST. A confounder in the TST is tail-climbing. The vast majority of studies using the TST perform the test during the mouse's sleep cycle. We hypothesized that mice would spend less time immobile in their wake cycle than in their sleep cycle. One strain of mouse, C57BL/6J (B6), spent more time immobile in its wake cycle than in its sleep cycle. A second strain of mouse, DBA2/J (D2), spent less time immobile in its wake cycle than in its sleep cycle. Both strains of mice were more likely to climb their tails in the wake cycle than in the sleep cycle. Our findings suggest that the outcome of the TST is affected by the assessment time; this is likely applicable to other behavioral assessment tests.

Involvement of nitric oxide–cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test

Clinical and preclinical data reported that ascorbic acid has antidepressant properties. The present study was designed to investigate the participation of l-arginine–NO–cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST) in mice. The antidepressant-like effect of ascorbic acid (1 mg/kg, p.o.) in the TST was prevented by the pre-treatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.001 mg/kg, i.p), 7-nitroindazole (25 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of ascorbic acid (0.1 mg/kg, p.o.) reduced the immobility time in the TST test when compared with either drug alone. None of the results in the TST appears to be due to a nonspecific locomotor effect. Our findings provide evidence that the effect of ascorbic acid in the TST involve an interaction with NMDA receptors and l-arginine–NO–cGMP pathway, contributing to the understanding of the mechanisms underlying the antidepressant-like effect of this vitamin.