13. FGF2 Gene is required for Antidepressant Treatment Effects

Author(s):  
Jessica MacGregor

gene in humans have been shown to predict non-responsiveness to antidepressant drugs; suggesting that FGF2 is required for antidepressants to work. In this study, we hypothesized that antidepressants will not work in rodents that lack the FGF2 gene. Hence, we tested antidepressant treatment in transgenic mice that had the FGF2 gene knocked out. Chronic unpredictable stress (CUS) has been used for several decades to produce a reliable depressive and anxious phenotype in mice. This study followed a CUS paradigm and used fluoxetine (Prozac) as antidepressant treatment. Mice received daily fluoxetine administration beginning on week three of CUS and continued until the end of week five to provide an antidepressant effect and reverse the effects of stress. To test for levels of anxiety and depression, a battery of behavioral tests was conducted which began from the least stressful (i.e. sucrose preference test, open field maze, elevated plus maze) to the most stressful test (forced swim test) to prevent testing carry-over effects. AnyMaze software was used to measure behavior in the open field and elevated plus mazes by recording the amount of time each mouse spent in certain parts of the maze. Future studies will examine brain changes associated with FGF2 gene deletion – particularly in astrocyte cells – which might be necessary for successful antidepressant action. Hopefully, this will elucidate novel therapeutic targets for antidepressant and anti-anxiety medication. 

2019 ◽  
Vol 12 (2) ◽  
pp. 981-988
Author(s):  
Venkata Naveen Kumar P. ◽  
Elango P. ◽  
Asmathulla S. ◽  
Kavimani S

The present study aimed at evaluating the effects of lycopene on CMS-induced depressive-like behavioral changes in Wistar rats. In present study, rodents were selected randomly and grouped in to seven groups. Each group consists of six animals. All the groups are subjected to chronic mild stress in an unpredictable manner except the control group, which is free from stress. Behavioral changes induced during chronic mild stress were assessed by conducting the behavioral tests like forced swim test, sucrose preferences test, elevated plus maze test and open field tests in screening depressant and anxiety activity. The data analysis showed chronic mild stress produced depressive and anxiogenic behavior in the experimental rats. A significant increase in the immobility time and decrease in sucrose consumption in sucrose preference test are noted in CMS and vehicle groups. Similarly, in an elevated plus maze a significant decrease in the entries in the open arm and decrease in central square entries, and rearing behavior and increase in the duration of immobility were observed in open field test.Lycopene treatment for 6-weeks significantly decreased immobility time and increased in sucrose consumption observed in the forced swim test and sucrose preference test respectively. Lycopene significantly increased number of entries in the open arm of elevated plus maze and decreased grooming and freezing behavior in open field method. lycopene supplemented dose of 5mg/kg showed an insignificant results in all the behavioral models (p>0.05).The data were expressed as Mean±SD.Data were analyzed and differences between the means were determined by one-way analysis of variance (ANOVA) Using graph pad prism version 5.03 statistical software. In all the tests, differences were considered significant if p<0.05 to be a statistical significant. lycopene possesses antidepressant and mild- anxiolytic activity which may be due to its antioxidant effect that might warrant further studies.


2017 ◽  
Vol 10 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Kristina Belovicova ◽  
Eszter Bogi ◽  
Kristina Csatlosova ◽  
Michal Dubovicky

AbstractAn animal model of human behavior represents a complex of cognitive and/or emotional processess, which are translated from animals to humans. A behavioral test is developed primarily and specifically to verify and support a theory of cognition or emotion; it can also be used to verify a theory of a psychopathology, but it is not developed for a particular type of psychopathology. The paper reviews tests commonly used in novel drug discovery research. Focus is especially on tests which can evaluate anxiety-like (open-field test, novelty suppressed feeding, elevated plus maze, light/dark box, stressinduced hyperthermia) and depression-like behaviors (forced swim test, tail suspension test, sucrose preference test) as they represent an important methodological tool in pre-clinical as well as in behavioral toxicology studies.


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 857
Author(s):  
Rongrong Li ◽  
Chiyuan Ma ◽  
Yue Xiong ◽  
Huashan Zhao ◽  
Yali Yang ◽  
...  

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant–like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.


2021 ◽  
Vol 11 ◽  
Author(s):  
Huiting Li ◽  
Yuanhui Li ◽  
Xiaofei Zhang ◽  
Guilin Ren ◽  
Liangfeng Wang ◽  
...  

The Aquilaria sinensis (Lour.) Gilg (CX)–Aucklandia costus Falc. (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX–MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 μL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic–pituitary–adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT1A mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.


2017 ◽  
Vol 41 (S1) ◽  
pp. s140-s140 ◽  
Author(s):  
Y. Bansal ◽  
A. Kuhad ◽  
R. Singh ◽  
P. Saroj

Aims and objectivesThe aim of study was to evaluate the pharmacotherapeutic efficacy of NDGA in experimental paradigm of depression i.e. olfactory bulbectomy (OB) specifically targeting kynurenine pathway.Materials and methodDepression like behaviours was induced in OB mice and evaluated by assessment of various behavioural (olfactory deficit test, forced swim test, splash test, open field test, sucrose preference test), biochemical (catalase, reduced glutathione, SOD, nitrite, MAO-A, MDA, corticosterone), inflammatory cytokines (TNF- α, IL-1β, IL-6, IFN-γ) levels and alterations in delta sleep was recorded using EEG. Kynurenine pathway metabolites were determined in plasma and brain using HPLC method. After 14 days post-surgery, olfactory bulbectomized (OBX) mice were administered nordihydroguaiaretic acid (5 mg/kg, 10 mg/kg and 25 mg/kg) daily i.p.ResultsWe have developed a new HPLC method for simultaneous estimation of monoamines and kynurenine pathway metabolites in plasma and brain samples of mice. Chronic treatment with nordihydroguaiaretic acid significantly restored all behavioural, biochemical and neurochemical alterations in OBX mice and increase in quinolinic acid and decrease in kynurenic acid point out the neurodegeneration hypothesis of depression.ConclusionNordihydroguaiaretic acid showed potent neuropharmacotherapeutic effect in OBX mice by virtue of its strong anti-oxidant, anti-inflammatory, anti-stress and by restoring quinolinic acid levels.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.


2011 ◽  
Vol 115 (4) ◽  
pp. 812-821 ◽  
Author(s):  
Jing Wang ◽  
Yossef Goffer ◽  
Duo Xu ◽  
David S. Tukey ◽  
D. B. Shamir ◽  
...  

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties. Methods The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression. Results Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.


2011 ◽  
Vol 26 (S2) ◽  
pp. 802-802
Author(s):  
N. Kokras ◽  
C. Dalla ◽  
K. Antoniou ◽  
Z. Papadopoulou-Daifoti

IntroductionSex differences have been described in depression and more recently in antidepressant response. Animal models and in particular the Forced Swim Test (FST), are widely used to investigate the behavioural response to stress and to antidepressant treatment.ObjectivesThe present study explored sex differences in the stress response during the FST and examined whether antidepressant treatment alleviates the sex-differentiated stress response.MethodsAdult male and female Wistar rats were subjected to a 15 min FST session and then treated with three injections of sertraline 10 mg/kg or vehicle at 0, 19 and 23 hours post-FST. Twenty-four hours after the first FST, they had a second 5 min FST session and their behaviour was recorded.ResultsVehicle-treated females exhibited 66% longer duration and 70% shorter latency of immobility than males, suggesting enhanced levels of despair. Sertraline did not significantly affect immobility, but exerted its antidepressant effect by elongating swimming duration in both sexes and shortening climbing behaviour in males only. In contrast, to vehicle-treated rats, no sex differences were observed in sertraline-treated rats in any of these behavioural parameters. However, sex-differences in head swinging behaviour, which is unaffected by sertraline treatment, were still observed in sertraline-treated rats.ConclusionsFemales appear more vulnerable than males to the FST, but the post-treatment organisation of FST behaviour is not sex-differentiated. Antidepressants seem to modulate the behavioural response in FST in a sex-specific way, due to sex differences in baseline FST performance. Consequently, the sex-differentiated stress response profile during FST is attenuated by antidepressant treatment.


2019 ◽  
Author(s):  
Chihiro Nakamoto ◽  
Meiko Kawamura ◽  
Ena Nakatsukasa ◽  
Rie Natsume ◽  
Keizo Takao ◽  
...  

AbstractThe GluD1 gene is associated with susceptibility for schizophrenia, autism, depression, and bipolar disorder. However, the function of GluD1 and how it is involved in these conditions remain elusive. In this study, we generated a GluD1-knockout (GluD1-KO) mouse line with a pure C57BL/6N genetic background and performed several behavioral analyses. Compared to a control group, GluD1-KO mice showed no significant anxiety-related behavioral differences, evaluated using behavior in an open field, elevated plus maze, a light-dark transition test, the resident-intruder test of aggression and sensorimotor gating evaluated by the prepulse inhibition test. However, GluD1-KO mice showed (1) hyper locomotor activity in the open field, (2) decreased sociability and social novelty preference in the three-chambered social interaction test, (3) impaired memory in contextual, but not cued fear conditioning tests, and (4) enhanced depressive-like behavior in a forced swim test. Pharmacological studies revealed that enhanced depressive-like behavior in GluD1-KO mice was restored by the serotonin reuptake inhibitors imipramine and fluoxetine, but not the norepinephrine transporter inhibitor desipramine. In addition, biochemical analysis revealed no significant difference in protein expression levels, such as other glutamate receptors in the synaptosome and postsynaptic densities prepared from the frontal cortex and the hippocampus. These results suggest that GluD1 plays critical roles in fear memory, sociability, and depressive-like behavior.


2021 ◽  
Author(s):  
Anna Donen ◽  
Tzuri Lifschytz ◽  
Gilly Wolf ◽  
Hagar Ben-Ari ◽  
Amit Lotan ◽  
...  

Aim: Spirulina is a microalga that is widely used as a food supplement and is regarded as having performance enhancing and health promoting properties. We conducted a preliminary evaluation of the possible antidepressant, anti-anxiety, pro-socialization and cognition-enhancing effects of Spirulina in mouse models. Methods: Sixty male BalbC mice aged 3 weeks were administered phycocyanin-rich Spirulina extract (PRSE, 545 mg/kg), fluoxetine (20 mg/kg) or water orally for 5 weeks. During the last 2 weeks of the experiment a series of behavioral-cognitive tests was performed to evaluate motor activity, antidepressant and anti-anxiety effects, socialization and cognitive effects. Effects of PRSE and fluoxetine were compared to those of water. Results: There was a significant effect of PRSE in the activity domain, manifesting as an increase in velocity in the open field (p=0.0007 vs. water). Fluoxetine significantly enhanced immobility in the tail suspension test and the forced swim test reflecting the known antidepressant effect of this compound, but not PRSE. There were no significant effects of PRSE in tests of anxiety, socialization or cognition. Conclusions: The most striking observation in this study was that PRSE significantly enhanced activity in the open field test. Further studies are indicated to confirm and extend this finding and investigate possible mechanisms of action. The results of the current study do not support sporadic reports of possible antidepressant or cognition-enhancing effects of PRSE. Nevertheless, additional studies are indicated using depression models rather than naive mice, alternative mouse strains, using additional cognitive tests, and administering higher PRSE doses.


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