The Anxiogenic Effects of Caffeine Do Not Potentiate Nicotine Withdrawal in an Elevated Plus Maze Model of Anxiety

Anxiety during nicotine withdrawal (NicW) is a key risk factor for smoking relapse. Semen Ziziphi Spinosae (SZS), which is a prototypical hypnotic-sedative herb in Oriental medicine, has been clinically used to treat insomnia and general anxiety disorders for thousands of years. Thus, the present study evaluated the effects of the aqueous extract of SZS (AESZS) on NicW-induced anxiety in male rats that received subcutaneous administrations of nicotine (Nic) (0.4 mg/kg, twice a day) for 7 d followed by 4 d of withdrawal. During NicW, the rats received four intragastric treatments of AESZS (60 mg/kg/d or 180 mg/kg/d). AESZS dose-dependently attenuated NicW-induced anxiety-like behaviors in the elevated plus maze (EPM) tests and 180 mg/kg/d AESZS inhibited NicW-induced increases in plasma corticosterone. Additionally, the protein and mRNA expressions of corticotropin-releasing factor (CRF) and CRF type 1 receptor (CRF1R) increased in the central nucleus of the amygdala (CeA) during NicW, but these changes were suppressed by 180 mg/kg/d AESZS. A post-AESZS infusion of CRF into the CeA abolished the attenuation of anxiety by AESZS and 180 mg/kg/d AESZS suppressed NicW-induced increases in norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the CeA. The present results suggest that AESZS ameliorated NicW-induced anxiety via improvements in CRF/CRF1R and noradrenergic signaling in the CeA.

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Estradiol promotes and progesterone reduces anxiety-like behavior produced by nicotine withdrawal in rats

10.1101/842252 ◽

2019 ◽

Author(s):

Rodolfo J. Flores ◽

Bryan Cruz ◽

Kevin P. Uribe ◽

Victor L. Correa ◽

Montserrat C. Arreguin ◽

...

Keyword(s):

Nicotinic Receptor ◽

Elevated Plus Maze ◽

Ovarian Hormones ◽

Nicotine Withdrawal ◽

Female Rats ◽

Intact Female ◽

Sham Surgery ◽

Ovx Rats ◽

Plus Maze

AbstractThe present study assessed sex differences and the role of ovarian hormones in the behavioral effects of nicotine withdrawal. Study 1 compared physical signs, anxiety-like behavior, and corticosterone levels in male, intact female, and ovariectomized (OVX) female rats during nicotine withdrawal. Estradiol (E2) and progesterone levels were also assessed in intact females that were tested during different phases of the 4-day estrous cycle. Study 2 assessed the role of ovarian hormones in withdrawal by comparing the same measures in OVX rats that received vehicle, E2, or E2+progesterone prior to testing. Briefly, rats received a sham surgery or an ovariectomy procedure. Fifteen days later, rats were prepared with a pump that delivered nicotine for 14 days. On the test day, rats received saline or the nicotinic receptor antagonist, mecamylamine to precipitate withdrawal. Physical signs and anxiety-like behavior were assessed on the elevated plus maze (EPM) and light-dark transfer (LDT) tests. During withdrawal, intact females displayed greater anxiety-like behavior and corticosterone levels as compared to male and OVX rats. Females tested in estrus (when E2 is relatively low) displayed less anxiety-like behavior and corticosterone versus all other phases. Anxiety-like behavior and corticosterone were positively correlated with E2 and negatively correlated with progesterone. Intact females displaying high E2/low progesterone displayed greater anxiety-like behavior and corticosterone as compared to females displaying low E2/high progesterone. Lastly, OVX-E2 rats displayed greater anxiety-like behavior than OVX-E2+progesterone rat. These data suggest that E2 promotes and progesterone reduces anxiety-like behavior produced by withdrawal.

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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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