Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat

AbstractObjective:Psilocybin is a serotonin receptor agonist with a therapeutic potential for treatment-resistant depression and other psychiatric illnesses. We investigated whether the administration of psilocybin had an antidepressant-like effect in a rat model of depression.Methods:Using the Flinders Sensitive Line (FSL) rat model of depression, we assessed the antidepressant-like effect of psilocin and psilocybin, measured as a reduction in immobility time in the forced swim test (FST). We measured locomotor activity in an open field test (OFT) to control for stimulant properties of the drugs. We performed a set of experiments to test different doses, treatment paradigms, and timing of the tests in relation to the drug administration.Results:Psilocin and psilocybin showed no effect on immobility, struggling, or swimming behaviour in the FST and no effect on locomotor activity in the OFT. FSL rats did show significantly more immobility than their control strain, the Flinders Resistant Line, as expected.Conclusion:Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.

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Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression

Acta Neuropsychiatrica ◽

10.1017/neu.2014.39 ◽

2014 ◽

Vol 27 (2) ◽

pp. 90-96 ◽

Cited By ~ 32

Author(s):

Nico Liebenberg ◽

Sâmia Joca ◽

Gregers Wegener

Keyword(s):

Nitric Oxide ◽

Frontal Cortex ◽

Rat Model ◽

Ex Vivo ◽

Forced Swim Test ◽

Signalling Pathway ◽

Guanosine Monophosphate ◽

Sensitive Line ◽

Pre Treatment ◽

Flinders Sensitive Line

ObjectiveWe investigated whether the nitric oxide (NO) precursor, l-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-d-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine.MethodsFlinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with l-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration.Resultsl-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by l-arginine.ConclusionBoth the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.

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Evaluation of Additive or Synergistic Effect of Piper nigram and Ocimum sanctum Extracts for their Antidepressant Activity

International Journal of Pharmaceutical Sciences Review and Research ◽

10.47583/ijpsrr.2021.v70i02.020 ◽

2021 ◽

Vol 70 (2) ◽

Author(s):

K. Mohana Rao ◽

Siva B. ◽

Mahendra U. ◽

Vinay K. ◽

A. Narendra Babu ◽

...

Keyword(s):

Locomotor Activity ◽

Forced Swim Test ◽

Antidepressant Activity ◽

Piper Nigrum ◽

Ocimum Sanctum ◽

Alcoholic Extract ◽

Swim Test ◽

Forced Swim ◽

Immobility Time ◽

Wide Range

Depression is a state of excessive sensitivity to criticism, fear of rejections, lack of self-interest, loss of pleasure. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. In recent times, research on the plants increased globally and so many plants provide the evidence to cure diseases. Ocimum sanctum, popularly known as Tulsi is one of the sacred herbs for Hindus in the Indian subcontinent. It has a versatile role in traditional medicine. The fruits of Piper nigrum are used to make black pepper. This hotly pungent spice is one of the earliest known and most widely used spices in the world today. Wide range of animal tests for antidepressant agents are commonly used. The Forced swim test and Tail suspension test in mice were mostly used. Hence in the present study Forced swim test was used as animal model of depression. In present study immobility time in Forced swim test was significantly decreased by a combination of Piper nigrum fruit extract and Ocimum sanctum extract treated groups compared to control group. The combination of extracts (50 mg/kg each) activity was comparable to standard drug Fluoxetine. Treatment with extracts does not modify the locomotor activity of mice, which indicates that they exert antidepressant effects without modifying significantly locomotor activity. Therefore, the present study confirms the combination of alcoholic extract of Piper nigrum (AEPN) fruit and aqueous extract of Ocimum sanctum (AEOS) possessing additive/synergistic antidepressant activity.

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Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500180 ◽

2018 ◽

Vol 46 (02) ◽

pp. 357-387 ◽

Cited By ~ 8

Author(s):

Dool-Ri Oh ◽

Yujin Kim ◽

Eun-Jin Choi ◽

Myung-A Jung ◽

Kyo-Nyeo Oh ◽

...

Keyword(s):

Locomotor Activity ◽

Signaling Pathway ◽

Restraint Stress ◽

Forced Swim Test ◽

Akt Signaling ◽

Antagonistic Effect ◽

Chronic Restraint Stress ◽

Akt Signaling Pathway ◽

Neuroprotective Effects ◽

Immobility Time

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

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EVALUATION OF ANTISTRESS ACTIVITY OF ETHANOLIC EXTRACT OF CHROMOLAENA ODORATA LEAVES IN ALBINO WISTAR RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i11.35452 ◽

2019 ◽

pp. 50-55

Author(s):

VANITA KANASE ◽

SANA SHAIKH

Keyword(s):

Locomotor Activity ◽

Wistar Rats ◽

Forced Swim Test ◽

Ethanolic Extract ◽

Force Swim Test ◽

Chromolaena Odorata ◽

Biochemical Alterations ◽

Swim Test ◽

Induced Stress ◽

Immobility Time

Objective: The objective of this study was to study the effect of ethanolic extract of Chromolaena odorata (EECO) Linn. on acute restraint stress (ARS)-induced stress-like behavior and biochemical alterations in albino Wistar rats. Methods: The ARS was induced by immobilizing the rats for a period of 12 h using rodent restraint device preventing them from any physical movement. Immediately, after 12 h rats were released and doses were given to each rat. 40 min post-release various behavioral parameters such as immobility time in force swim test and tail suspension test (TST), locomotor activity in open field test (OFT), and oxidative stress parameters and biochemical alterations in rat brain tissue were also performed. Statistical Analysis: Expression of data was done as mean±standard error of mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett’s test. p<0.05 was considered statistically significant. Results: Experimental findings revealed that rats subjected to ARS exhibited significant increase in immobility time in forced swim test and TST models, decrease in locomotor activity in OFT model, and increase in malondialdehyde formation and impaired superoxide dismutase, and catalase activities in hippocampus and cerebral cortex as compared to non-stressed rats. EECO treatment (250 mg/kg and 500 mg/kg) significantly attenuated immobility time, locomotion, and restored the antioxidant enzymes after ARS. Conclusion: EECO significantly alleviated ARS-induced stress-like behavior.

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Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2010.05.029 ◽

2010 ◽

Vol 34 (6) ◽

pp. 1075-1084 ◽

Cited By ~ 8

Author(s):

Olga Kotsovolou ◽

Magnus Ingelman-Sundberg ◽

Matti A. Lang ◽

Marios Marselos ◽

David H. Overstreet ◽

...

Keyword(s):

Rat Model ◽

Hepatic Drug ◽

Sensitive Line ◽

Flinders Sensitive Line

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Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the flinders sensitive line rat model of depression: Effect of ketamine

Synapse ◽

10.1002/syn.21940 ◽

2016 ◽

Vol 71 (1) ◽

pp. 37-45 ◽

Cited By ~ 4

Author(s):

Kristian Gaarn Du Jardin ◽

Heidi Kaastrup Müller ◽

Connie Sanchez ◽

Gregers Wegener ◽

Betina Elfving

Keyword(s):

Gene Expression ◽

Rat Model ◽

Glutamatergic Neurotransmission ◽

Depression Effect ◽

Sensitive Line ◽

Flinders Sensitive Line

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Brain Arachidonic Acid Incorporation and Turnover are not Altered in the Flinders Sensitive Line Rat Model of Human Depression

Neurochemical Research ◽

10.1007/s11064-015-1719-6 ◽

2015 ◽

Vol 40 (11) ◽

pp. 2293-2303

Author(s):

Helene Blanchard ◽

Lisa Chang ◽

Amir H. Rezvani ◽

Stanley I. Rapoport ◽

Ameer Y. Taha

Keyword(s):

Arachidonic Acid ◽

Rat Model ◽

Acid Incorporation ◽

Sensitive Line ◽

Flinders Sensitive Line

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Repeated prenatal stress sessions produce changes in exploration and despair detectable at weanling in wistar rats

European Psychiatry ◽

10.1016/s0924-9338(11)73280-1 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1576-1576

Author(s):

B. Bernal-Morales ◽

C.M. Contreras ◽

J. Cueto-Escobedo ◽

G. Guillén-Ruiz

Keyword(s):

Locomotor Activity ◽

Open Field ◽

Prenatal Stress ◽

Forced Swim Test ◽

Control Group ◽

Stress Group ◽

Forced Swim ◽

Immobility Time ◽

Effects Of Stress ◽

Postnatal Stress

IntroductionDuring gestation and maternal behavior, some physiological events can protect the dam and offspring, but explanations for such phenomena are partially unknown. The effects of stress during prenatal development and infancy can be studied in controlled laboratory conditions.ObjectiveTo determine the pre- and postnatal effects of stress on coping strategies in weanling rats subjected to the open field and forced swim tests after their dams are subjected to stress during gestation.MethodRats aged 21 postnatal days (PND) were assigned to either a Control group (n = 36; offspring from intact dams during gestation) or a Prenatal stress group (n = 36; offspring from dams forced to swim during 5 min sessions on gestational days 1, 7, 14, and 19). Both groups were tested in the open field to evaluate locomotor activity and rearing. In another experiment, PND21 intact rats assigned to a Control group (n = 26) or Postnatal stress group (n = 35) were subjected to restraint stress for 6 min prior to the tests and were later evaluated in the forced swim test.ResultsLocomotor activity (p < 0.026) and rearing (p < 0.001) were lower in the Prenatal stress group compared with the Control group. The latency to first immobility was shorter (p < 0.008), and the total immobility time was longer (p < 0.005) in the Postnatal stress group than Control group.ConclusionStress exposure during gestation produces detectable changes during weanling, consisting of reduced exploratory activity and susceptibility to despair.

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Sirtuins and Neuropeptide y downregulation in Flinders Sensitive Line Rat Model of Depression

Acta Neuropsychiatrica ◽

10.1017/neu.2021.36 ◽

2021 ◽

pp. 1-19

Author(s):

Miranda Stiernborg ◽

Paschalis Efstathopoulos ◽

Andreas Lennartsson ◽

Catharina Lavebratt ◽

Aleksander A. Mathé

Keyword(s):

Rat Model ◽

Histone Deacetylases ◽

Sirtuin 1 ◽

Model Organisms ◽

Age Related ◽

Age Dependent ◽

Sensitive Line ◽

And Control ◽

Temporal Trajectory ◽

Flinders Sensitive Line

Abstract Objective: Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3 month old and 14-15 month old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. Methods: Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. Results: PFC. Sirt1 expression was decreased in FSL (p=0.001). An interaction between age and genotype was found (p=0.032); young FSL had lower Sirt1 with respect to both age (p=0.026) and genotype (p=0.001). Sirt2 was lower in FSL (p=0.003). Npy mRNA was downregulated in FSL (p=0.001) but did not differ between the young and old rat groups. Hippocampus.Sirt1 was reduced in young FSL compared to young FRL (p=0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p=0.003). Effects of ageing could not be investigated due to loss of samples. Conclusions: i. This is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression ; ii. The changes are age dependent; iii. Sirtuins are potential targets for treatment of age-related neurodegenerative diseases.

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