Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest

Object Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus. Methods A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxlyase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining. Results The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y–immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxlyase–immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats. Conclusions These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the central dopamine system.

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Preventing adolescent synaptic pruning in mouse prelimbic cortex via local knockdown of α4βδ GABAA receptors increases anxiety response in adulthood

Scientific Reports ◽

10.1038/s41598-021-99965-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Matthew R. Evrard ◽

Michael Li ◽

Hui Shen ◽

Sheryl S. Smith

Keyword(s):

Gabaa Receptors ◽

Adolescent Females ◽

Prelimbic Cortex ◽

Spine Density ◽

Knock Out ◽

Plus Maze ◽

Anxiety Response ◽

Global And Local ◽

The Impact ◽

Synaptic Pruning

AbstractAnxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of α4βδ GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by α4 knock-out, suggesting that α4βδ-induced reductions in kalirin7 underlie pruning. Increased spine density due to local α4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies.

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Anxiolytic effects of fractions obtained from Passiflora incarnata L. in the elevated plus maze in mice

Planta Medica ◽

10.1055/s-0030-1264635 ◽

2010 ◽

Vol 76 (12) ◽

Author(s):

C Sampath ◽

M Holbik ◽

L Krenn ◽

V Butterweck

Keyword(s):

Elevated Plus Maze ◽

Plus Maze ◽

Passiflora Incarnata

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Faculty Opinions recommendation of Individual differences in elevated plus-maze exploration predicted progressive-ratio cocaine self-administration break points in Wistar rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1091235.544645 ◽

2007 ◽

Author(s):

Trevor W Robbins

Keyword(s):

Individual Differences ◽

Wistar Rats ◽

Elevated Plus Maze ◽

Progressive Ratio ◽

Self Administration ◽

Plus Maze ◽

Break Points

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Neuropharmacological Characterization of Dioclea altissima Seed Lectin (DAL) in Mice: Evidence of Anxiolytic-like Effect Mediated by Serotonergic, GABAergic Receptors and NO Pathway

Current Pharmaceutical Design ◽

10.2174/1381612826666200331093207 ◽

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 ◽

...

Keyword(s):

Structural Integrity ◽

Elevated Plus Maze ◽

Biological Activities ◽

Plant Lectins ◽

Plus Maze ◽

Marble Burying ◽

Gabaergic Receptors ◽

The Central Nervous System ◽

Hole Board

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.

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Anticonvulsant, Anxiolytic and Antidepressant Properties of the β-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems

Current Molecular Pharmacology ◽

10.2174/1874467213666200510004622 ◽

2020 ◽

Vol 14 (1) ◽

pp. 36-51 ◽

Cited By ~ 1

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

Keyword(s):

Receptor Antagonist ◽

Molecular Mechanisms ◽

Elevated Plus Maze ◽

Feeding Test ◽

Swiss Mice ◽

Elevated Plus Maze Test ◽

Maze Test ◽

Plus Maze ◽

Gabaergic Receptors ◽

Pre Treatment

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.

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Replacing a Palatable High-Fat Diet with a Low-Fat Alternative Heightens κ-Opioid Receptor Control over Nucleus Accumbens Dopamine

Nutrients ◽

10.3390/nu13072341 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2341

Author(s):

Conner W. Wallace ◽

Nari S. Beatty ◽

Sarah A. Hutcherson ◽

Heather A. Emmons ◽

Madison C. Loudermilt ◽

...

Keyword(s):

Weight Loss ◽

Nucleus Accumbens ◽

High Fat Diet ◽

Elevated Plus Maze ◽

High Fat ◽

Food Cravings ◽

Fast Scan Cyclic Voltammetry ◽

Diet Induced Obesity ◽

Plus Maze ◽

Weight Loss Interventions

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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Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test

Molecular Brain ◽

10.1186/s13041-020-00721-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Hirotaka Shoji ◽

Tsuyoshi Miyakawa

Keyword(s):

Elevated Plus Maze ◽

Plasma Corticosterone ◽

Illumination Level ◽

Test Battery ◽

Lower Percentage ◽

Behavioral Tests ◽

Elevated Plus Maze Test ◽

Maze Test ◽

Plus Maze ◽

Corticosterone Response

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.

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