scholarly journals Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Dominik K. E. Beyer ◽  
Annika Mattukat ◽  
Nadja Freund
Keyword(s):  
Bipolar Disorder ◽  
Animal Model ◽  
Elevated Plus Maze ◽  
D1 Receptor ◽  
Adult Rats ◽  
Male Adult ◽  
Respective Control ◽  
Plus Maze ◽  
Inflammatory State ◽  
Anxiety Behavior

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.

scholarly journals Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

2020 ◽  
Author(s):  
Dominik K E Beyer ◽  
Annika Mattukat ◽  
Nadja Freund
Keyword(s):  
Bipolar Disorder ◽  
Immune System ◽  
Lentiviral Vector ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Male Adult ◽  
Over Expression ◽  
Tissue Manipulation ◽  
Inflammatory State ◽  
Anxiety Behavior

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. Patients with bipolar disorder show alternations in the dopamingergic and immune system. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is increased in plasma samples, imaging studies and post mortem tissue. Manipulation of the D1R in the medial prefrontal cortex (mPFC) e.g. results in BD-like behavior. The purpose of the study is the investigation of the influence of D1R over-expression and its termination on the immune system and anxiety behavior in rats.Methods – Expression of the gene for D1R in glutamatergic neurons within the mPFC of male, adult rats was manipulated through an inducible (Tet.On) lentiviral vector. Anxiety behavior was studied in the elevated plus maze and marble burying test in ‘ON’ (D1R over-expression) and ‘OFF’ (termination of D1R over-expression) states. IL-6-positive cells were counted to identify the inflammatory state within several subregions of the hippocampus.Results - D1R ‘OFF’ subjects buried more marbles compared to D1R ‘ON’ and their respective control animals indicating an increased anxiety behavior. D1R ‘OFF’ animals reflected an elevated pro-inflammatory state in the hippocampus, in the CA3 and dentate gyrus especially. 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 molecular findings support the association of D1R’s impact on anxiety and inflammation. In addition, by confirming an involvement of IL-6, the new animal model for bipolar disorder has been further validated.

Age-Related Differences in Elevated Plus Maze Behavior between Adolescent and Adult Rats

2004 ◽  
Vol 1021 (1) ◽  
pp. 427-430 ◽  
Author(s):  
TAMARA L. DOREMUS ◽  
ELENA I. VARLINSKAYA ◽  
LINDA PATIA SPEAR
Keyword(s):  
Elevated Plus Maze ◽  
Adult Rats ◽  
Age Related ◽  
Plus Maze

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium

2021 ◽  
Vol 22 ◽  
Author(s):  
Trina Sengupta ◽  
Sutirtha Ghosh ◽  
Archana Gaur T. ◽  
Prasunpriya Nayak
Keyword(s):  
Body Weight ◽  
Young Adult ◽  
Adult Female ◽  
Developmental Stages ◽  
Elevated Plus Maze ◽  
Age Groups ◽  
Female Rats ◽  
Acute Exposure ◽  
Adult Rats ◽  
Plus Maze

Background: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium’s effect on anxiety in rodents at the different developmental stages is inconsistent. Aims: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. Objective: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. Methods: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. Results: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. Conclusion: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

scholarly journals Sensitivity to diazepam after a single session of forced swim stress in weaning Wistar rats

2018 ◽  
Vol 68 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Blandina Bernal-Morales ◽  
Gabriel Guillén-Ruiz ◽  
Jonathan Cueto-Escobedo ◽  
Juan Francisco Rodríguez-Landa ◽  
Carlos M. Contreras
Keyword(s):  
Wistar Rats ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Clinical Applications ◽  
Minimum Effective Dose ◽  
Single Session ◽  
Adult Rats ◽  
Stressed Group ◽  
Plus Maze ◽  
Forced Swim Stress

Abstract The present study investigated the sensitivity to stress and diazepam in weaning (21-day old) Wistar rats. A single 15-min session of forced swimming was used to induce anxiety-like behavior. The group that was forced to swim exhibited an increase in anxiety-like behavior in the elevated plus maze (EPM) and open field test (OFT) compared to the non-stressed group. Diazepam (1 h before the tests) reduced anxiety-like behavior in rats forced to swim compared to the vehicle stressed group. The dose-response curve for diazepam indicated that the 0.5 mg kg−1 dose (1 h before the EPM and OFT) was the minimum effective dose in reducing anxiety-like behavior without altering locomotor activity in weaning rats. These results indicate that weaning rats can develop anxiety-like behavior after a brief, single session of stress, and that rats at this age are seemingly more sensitive to diazepam than adult rats, which may be taken into account for clinical applications.

Agmatine induces anxiolysis in the elevated plus maze task in adult rats

2003 ◽  
Vol 141 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Daniel Lavinsky ◽  
Nice Sarmento Arteni ◽  
Carlos Alexandre Netto
Keyword(s):  
Elevated Plus Maze ◽  
Maze Task ◽  
Adult Rats ◽  
Plus Maze

scholarly journals Intergenerational Effects of Sevoflurane in Young Adult Rats

2019 ◽  
Vol 131 (5) ◽  
pp. 1092-1109 ◽  
Author(s):  
Ling-Sha Ju ◽  
Jiao-Jiao Yang ◽  
Ning Xu ◽  
Jia Li ◽  
Timothy E. Morey ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Prepulse Inhibition ◽  
Germ Cells ◽  
Elevated Plus Maze ◽  
Acoustic Startle ◽  
Chloride Ion ◽  
Male Rats ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Plus Maze

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sevoflurane administered to neonatal rats induces neurobehavioral abnormalities and epigenetic reprogramming of their germ cells; the latter can pass adverse effects of sevoflurane to future offspring. As germ cells are susceptible to reprogramming by environmental factors across the lifespan, the authors hypothesized that sevoflurane administered to adult rats could induce neurobehavioral abnormalities in future offspring, but not in the exposed rats themselves. Methods Sprague-Dawley rats were anesthetized with 2.1% sevoflurane for 3 h every other day between postnatal days 56 and 60. Twenty-five days later, exposed rats and nonexposed controls were mated to produce offspring. Results Adult male but not female offspring of exposed parents of either sex exhibited deficiencies in elevated plus maze (mean ± SD, offspring of both exposed parents vs. offspring of control parents, 35 ± 12 vs. 15 ± 15 s, P < 0.001) and prepulse inhibition of acoustic startle (offspring of both exposed parents vs. offspring of control parents, 46.504 ± 13.448 vs. 25.838 ± 22.866%, P = 0.009), and increased methylation and reduced expression of the potassium ion-chloride ion cotransporter KCC2 gene (Kcc2) in the hypothalamus. Kcc2 was also hypermethylated in sperm and ovary of the exposed rats. Surprisingly, exposed male rats also exhibited long-term abnormalities in functioning of the hypothalamic-pituitary-gonadal and -adrenal axes, reduced expression of hypothalamic and hippocampal Kcc2, and deficiencies in elevated plus maze (sevoflurane vs. control, 40 ± 24 vs. 25 ± 12 s, P = 0.038) and prepulse inhibition of startle (sevoflurane vs. control, 39.905 ± 21.507 vs. 29.193 ± 24.263%, P < 0.050). Conclusions Adult sevoflurane exposure affects brain development in male offspring by epigenetically reprogramming both parental germ cells, while it induces neuroendocrine and behavioral abnormalities only in exposed males. Sex steroids may be required for mediation of the adverse effects of adult sevoflurane in exposed males.

scholarly journals EFFECT OF DIFFERENT STATINS IN ANIMAL MODEL OF ANXIETY IN WISTAR RATS

2018 ◽  
Vol 11 (10) ◽  
pp. 369
Author(s):  
Jyothsna Vc ◽  
Balaji O ◽  
Bharti Chogtu
Keyword(s):  
Animal Model ◽  
Anxiety Disorder ◽  
Open Field ◽  
Generalized Anxiety Disorder ◽  
Field Model ◽  
Elevated Plus Maze ◽  
Saline Group ◽  
Generalized Anxiety ◽  
Plus Maze ◽  
Group 5

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. 

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