A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze

2003 ◽  
Vol 463 (1-3) ◽  
pp. 163-175 ◽  
Author(s):  
S. Mechiel Korte ◽  
Sietse F. De Boer
Author(s):  
Jyothsna Vc ◽  
Balaji O ◽  
Bharti Chogtu

Objective: Pleiotropic mechanisms of statins have been explored in treating neurological disorders such as generalized anxiety disorder and depression. Hence, the aim of the present study is to evaluate the effect of different statins in animal model of anxiety in Wistar rats.Methods: Sixty rats were divided into five groups of 6 rats each for each model. Two models were used, elevated plus maze and open-field model. Grouping is as follows: Group 1 - normal control (0.9% saline), Group 2 - alprazolam 0.5 mg/kg, Group 3 - atorvastatin 10 mg/kg, Group 4 - rosuvastatin 10 mg/kg, and Group 5 - pitavastatin 10 mg/kg. All drugs were given orally for 30 days.Results: In open-field model and in elevated plus maze, alprazolam, atorvastatin, rosuvastatin, and pitavastatin in comparison with control showed significant antianxiety effect (p<0.01 and p<0.001), respectively.Conclusion: Hence, further clinical trials can be done to see the effect of various statins on generalized anxiety disorder in comparison with standard antianxiety drugs. 


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Dominik K. E. Beyer ◽  
Annika Mattukat ◽  
Nadja Freund

Abstract Background Prefrontal dopamine D1 receptor (D1R) mediates behavior related to anxiety, reward and memory, and is involved in inflammatory processes, all of which are affected in bipolar disorder. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is increased in patients with bipolar disorder in plasma samples, imaging studies and postmortem tissue and is an indicator for an inflammatory state. We could previously show that lentiviral overexpression of D1R in the medial prefrontal cortex (mPFC) of male adult rats and its termination induces bipolar disorder-like behavior. The purpose of this study was to investigate anxiety and the role of the immune system, specifically IL-6 positive neurons in this animal model. Due to its high density of inflammatory mediator receptors and therewith sensibility to immune activation, the hippocampus was investigated. Methods Expression of the gene for D1R in glutamatergic neurons within the mPFC of male, adult rats was manipulated through an inducible lentiviral vector. Animals over-expressing the gene (mania-like state), after termination of the expression (depressive-like) and their respective control groups were investigated. Anxiety behavior was studied in the elevated plus maze and marble burying test. Furthermore, IL-6-positive cells were counted within several subregions of the hippocampus. Results D1R manipulation in the mPFC had only mild effects on anxiety behavior in the elevated plus maze. However, subjects after termination buried more marbles compared to D1R over-expressing animals and their respective control animals indicating elevated anxiety behavior. In addition, animals in the depressive-like state showed higher numbers of IL-6 positive cells reflecting an elevated pro-inflammatory state in the hippocampus, in the CA3 and dentate gyrus. Consistently, inflammatory state in the whole hippocampus and anxiety behavior correlated positively, indicating a connection between anxiety and inflammatory state of the hippocampus. Conclusions Behavioral and neurobiological findings support the association of manipulation of the D1R in the mPFC on anxiety and inflammation in the hippocampus. In addition, by confirming changes in the inflammatory state, the proposed animal model for bipolar disorder has been further validated.


Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 601
Author(s):  
Juan Pablo Damián ◽  
Lucia Vázquez Alberdi ◽  
Lucía Canclini ◽  
Gonzalo Rosso ◽  
Silvia Olivera Bravo ◽  
...  

Charcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior profile of TrJ/+ and +/+ (wild-type) in open-field and elevated-plus-maze anxiety tests. In these tests, TrJ/+ showed an exclusive head shake movement, a lower frequency of rearing, but a greater frequency of grooming. In elevated-plus-maze, TrJ/+ defecate more frequently, performed fewer total entries, and have fewer entries to closed arms. These hippocampus-associated behaviors in TrJ/+ are consistent with increased anxiety levels. The expression of pmp22 and soluble PMP22 were evaluated in E17-hippocampal neurons and adult hippocampus by in situ hybridization and successive immunohistochemistry. Likewise, the expression of pmp22 was confirmed by RT-qPCR in the entire isolated hippocampi of both genotypes. Moreover, the presence of aggregated PMP22 was evidenced in unmasked granular hippocampal adult neurons and shows genotypic differences. We showed for the first time a behavior profile trait associated with anxiety and a differential expression of pmp22/PMP22 in hippocampal neurons of TrJ/+ and +/+ mice, demonstrating the involvement at the central level in an animal model of peripheral neuropathy (CMT1E).


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
C Sampath ◽  
M Holbik ◽  
L Krenn ◽  
V Butterweck

2020 ◽  
Vol 26 (31) ◽  
pp. 3895-3904
Author(s):  
João R.C. Araújo ◽  
Adriana R. Campos ◽  
Marina de Barros M.V. Damasceno ◽  
Sacha A.A.R. Santos ◽  
Maria K.A. Ferreira ◽  
...  

Background: Plant lectins have shown promising biological activities in the central nervous system (CNS). Objective: This study evaluated the effect of DAL, a lectin isolated from the seeds of the Dioclea altissima species, having binding affinity to D-glucose or D-mannose residues, on mice behavior. Methods: Mice (n=6/group) were treated (i.p.) with DAL (0.25, 0.5 or 1 mg/kg) or vehicle and subjected to several tests (open field/OFT, marble-burying/MBT, hole-board/HBT, elevated plus maze/PMT, tail suspension/ TST, forced swimming/FST or rotarod/RRT). Pizotifen, cyproheptadine, flumazenil, L-NAME, 7-NI, Larginine or yohimbine were administered 15 min before DAL (0.5 mg/kg) and the animals were evaluated on PMT. It was also verified whether the DAL effect depended on its structural integrity and ability to interact with carbohydrates. Results: The results showed there were no neurobehavioral changes in the mice at the RRT, FST and locomotion in the OFT. DAL (0.25, 0.5 or 1 mg/kg) increased the behavior of grooming and rearing in the OFT, head dips in the HBT, pedalling in the TST and decreased the number of marbles hidden in the MBT. In the PMT, DAL (0.25, 0.5 and 1 mg/kg) and Diazepam increased the frequency of entries in the open arms and the time of permanence in the open arms without affecting the locomotor activity. The effect of DAL was dependent on carbohydrate interaction and protein structure integrity and it prevented by pizotifen, cyproheptadine, flumazenil, L-NAME and 7-NI, but not by L-arginine or yohimbine. Conclusion: DAL was found to have an anxiolytic-like effect mediated by the 5-HT and GABAergic receptors and NO pathway.


2020 ◽  
Vol 14 (1) ◽  
pp. 36-51 ◽  
Author(s):  
George L. da Silva Oliveira ◽  
José C. Correia L. da Silva ◽  
Ana P. dos Santos C. L da Silva ◽  
Chistiane M. Feitosa ◽  
Fernanda R. de Castro Almeida

Background: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with β-caryophyllene is still little discussed. Objectives: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of β-caryophyllene (β-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained. Methods: This study evaluated the neurobehavioral effects of β-CBP using the open field test, rota-rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models. Results:: The results demonstrated that the neuropharmacological activities of β-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of β-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of β-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500- 750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of β-CBP. Conclusion: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of β-CBP in female Swiss mice.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2341
Author(s):  
Conner W. Wallace ◽  
Nari S. Beatty ◽  
Sarah A. Hutcherson ◽  
Heather A. Emmons ◽  
Madison C. Loudermilt ◽  
...  

Diet-induced obesity reduces dopaminergic neurotransmission in the nucleus accumbens (NAc), and stressful weight loss interventions could promote cravings for palatable foods high in fat and sugar that stimulate dopamine. Activation of κ-opioid receptors (KORs) reduces synaptic dopamine, but contribution of KORs to lower dopamine tone after dietary changes is unknown. Therefore, the purpose of this study was to determine the function of KORs in C57BL/6 mice that consumed a 60% high-fat diet (HFD) for six weeks followed by replacement of HFD with a control 10% fat diet for one day or one week. HFD replacement induced voluntary caloric restriction and weight loss. However, fast-scan cyclic voltammetry revealed no differences in baseline dopamine parameters, whereas sex effects were revealed during KOR stimulation. NAc core dopamine release was reduced by KOR agonism after one day of HFD replacement in females but after one week of HFD replacement in males. Further, elevated plus-maze testing revealed no diet effects during HFD replacement on overt anxiety. These results suggest that KORs reduce NAc dopamine tone and increase food-related anxiety during dietary weight loss interventions that could subsequently promote palatable food cravings and inhibit weight loss.


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