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Preclinical Antidepressant-Like Effects of Terpenes, Polyphenolics, and Other Non-Flavonoid Phytochemicals
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
β-Caryophyllene, a CB2 receptor agonist, is a bicyclic sesquiterpene found in clove oil, the oil from the stems and flowers of Syzygium aromaticum, cannabis, rosemary, and hops.45 In several studies, it has been found to have antidepressant-like effects in mice through decreases in immobility times in the forced swim and tail suspension tests. It also exhibits anxiolytic like effects in mice in the elevated plus maze, open field test, and marble burying tests.46 In one study, the antidepressantlike effects of chronically administered β-caryophyllene in mice were accompanied by increases in hippocampal levels of BDNF.47
Animal Models of Anxiety and Anxiolytic Drug Action
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
Dallas Treit, Aldemar Degroot, Akeel Shah
Gyertyan [96] suggested that marble burying in mice is not burying behavior per se, but rather digging/burrowing behavior, a species-typical response in mice that occurs in the absence of any observable aversive or threatening stimulus. In this sense, digging behavior might be more analogous to compulsive behavior in humans and thus mouse digging may represent a model of obsessive-compulsive disorder [96]. Although some of the pharmacological data reviewed above might be consistent with this view, insofar as certain antiobsessional compounds (e.g., clomipramine) were effective in suppressing marble burying, further work is needed before this hypothesis can be supported.
Nonclassical Ion Channels in Depression
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
In both animal and human studies, elevated transcription of Trek2 mRNA has been observed in the main anatomic loci of anxiety-related behavior, i.e. the hippocampus and amygdala104–106. The TREK1 inhibitor spadin produces a satisfactory antidepressant effect via enhanced phosphorylation of cAMP response element-binding protein and neurogenesis in the hippocampus. Furthermore, Trek1-deficient mice treated with spadin had a depression-resistant phenotype, although an acute treatment of spadin did not alleviate anxiety-related behaviors107. These findings agreed with the former results that showed Trek1-deficient mice do not exhibit an anxiety-resistant phenotype92. Given the relationship between TREK1 and sortilin, examination of Sort1-deficient mice revealed a corticosterone-independent anxiety-like behavior in various anxiety-related behavioral screens, such as the marble burying and the light-dark tests108. Additionally, the genetic ablation of Trek led to the discovery of its gender-dependent influence on anxious behaviors, as female Trek2-deficient mice spent more time than males and Trek1/2/Traak−/− mice spent significantly more time than wild type in the center of the OF, and also displayed fewer anxiety behaviors. However, Trek2-deficient mice and Trek1/2/Traak−/− mice behaved like the wild-type controls in the EPM and light/dark box tests, suggesting that neither genotype nor gender were contributing factors to performance in these tests96. In contrast with the results of experiments conducted with animals, riluzole, a putative activator of TREK1 channels109, may represent a promising direction for future treatment of mood and anxiety disorders in humans110. However, there is currently insufficient information regarding TREK1 to be considered a reliable target of treatments for anxiety.
Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission
Published in Inhalation Toxicology, 2023
María-de-los-Angeles Andrade-Oliva, Yazmín Debray-García, Guadalupe-Elide Morales-Figueroa, Juan Escamilla-Sánchez, Omar Amador-Muñoz, Raúl V. Díaz-Godoy, Michael Kleinman, Benjamín Florán, José-Antonio Arias-Montaño, Andrea De Vizcaya-Ruiz
An open arena is considered an averse novel environment for rodents, and it presents stressors inherent to open spaces; this test requires allowing rats to explore their environment (Carter and Shieh 2015). Our results showed decreased exploratory activity in rats exposed to FP or UFP, and this effect was observed within the first 5 min; these results correlate with emotional reactivity as evidenced by thigmotaxis (wall touching) and avoidance of the central area (Figures 1(A) and 2(F)), which was consistent with the notion that mice prefer being near a protective wall rather than exposed to danger in an open space. Reduced activity in the center of the arena was also reported in mice exposed to PM2.5 for 10 months (Fonken et al. 2011), and this behavior could be related to anxiety because animals in an anxious stress-like state spend less time in central areas and move closer to walls (Gogas et al. 2007). Microinfusion of the general D2R antagonist sulpiride in the striatum, which mimics the previously reported reduction in striatal D2R signaling (Andrade-Oliva et al. 2018), induces anxiety in rats (Nguyen et al. 2019). Further research addressing more specific anxiety-like behaviors with tests such as the elevated plus maze, fear conditioning, forced swimming, marble burying, and tail suspension tests are needed.
Toxicological evaluation of ethanolic extract of leaves from Doliocarpus dentatus in Swiss mice
Published in Drug and Chemical Toxicology, 2022
Lidiane Schultz Branquinho, Maria Helena Verdan, Elisangela dos Santos, Luis Fernando Benitez Macorini, Rafael Souza Maris, Angela Midori Kuraoka-Oliveira, Flávia Barbieri Bacha, Claudia Andrea Lima Cardoso, Arielle Cristina Arena, Saulo Euclides Silva-Filho, Cândida Aparecida Leite Kassuya
Products from natural origins, similar to many medications (Kessing et al.2020), can also have adverse effects, such as a depressive-like behavior. In addition to the toxic potential, the ability of EEDd to induce depression and anxiety-like behavior was investigated. Screening for testing drugs with depressive effects can be conducted through the tail suspension test. In this model, animals are suspended by the tail in an inescapable situation, in which they try to escape through vigorous activity and when they become immobile, they demonstrate a behavioral symptom of despair. Substances that increase the immobility time of animals are known to have depressive effects in humans (Dougnon and Ito 2020). The daily administration of EEDd (75, 150 and 300 mg/kg) did not increase the immobility time of the animals, therefore, a depressive-like behavior was not detected. The elevated plus maze and the marble burying tests were performed to assess anxiety and depression-like behavior, which are based on the exposure of the animals to a stressful condition. The elevated plus maze test assesses the aversion behavior of mice when entering an open arena, whereas the test of hiding spheres is based on the tendency of the animal to bury glass balls, since these behaviors are related to anxiety (De Almeida et al. 2012, Zhang et al. 2020). Our results showed that the exposure to EEDd for 28 days did not induce anxiety-like behavior in male and female mice.
The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota
Published in Tissue Barriers, 2022
Alba Miranda-Ribera, Gloria Serena, Jundi Liu, Alessio Fasano, Marcy A. Kingsbury, Maria R. Fiorentino
The Marble Burying test measures obsessive/compulsive/repetitive behavior, as a paradigm of the ethologically natural behavior of defensive burying.112–114 Regular housing cages (28x20x12 cm) were filled with 7 cm of autoclaved, and evenly distributed bedding material (Sani-chips®). Twenty Marbles (Fisher Science Education TM Glass Marbles #S04581, 1.42 cm) were placed equidistant in 4 parallel lines with alternating colors of black and blue. Mice were placed in the center of the cage and free to interact with the marbles. After 20 minutes, animals were removed carefully so as not to disturb the bedding and/or the marbles and the number of buried marbles was counted. Marbles were considered buried when at least 2/3 of their volume was covered by bedding material.