A mixture of eight fatty acids (linoleic, palmitic, stearic, myristic, elaidic, lauric, oleic, and palmitoleic acids) at similar concentrations identified in human amniotic fluid produces anxiolytic-like effects comparable to diazepam in Wistar rats. However, individual effects of each fatty acid remain unexplored. In Wistar rats, we evaluated the separate action of each fatty acid at the corresponding concentrations previously found in human amniotic fluid on anxiety-like behaviour. Individual effects were compared with vehicle, an artificial mixture of the same eight fatty acids, and a reference anxiolytic drug (diazepam, 2 mg/kg). Myristic acid, the fatty acid mixture, and diazepam increased the time spent in the open arms of the elevated plus maze and reduced the anxiety index compared with vehicle, without altering general locomotor activity. The other fatty acids had no effect on anxiety-like behaviour, but oleic acid reduced locomotor activity. Additionally, myristic acid produced anxiolytic-like effects only when the concentration corresponded to the one identified in human amniotic fluid (30 ????g/mL) but did not alter locomotor activity. We conclude that of the eight fatty acids contained in the fatty acid mixture, only myristic acid produces anxiolytic-like effects when administered individually at a similar concentration detected in human amniotic fluid.

The phytoestrogen genistein produces anxiolytic-like effects in ovariectomized rats, which highlights its potential therapeutic effect in ameliorating anxiety in surgical menopausal women. However, no studies have directly compared the effects of identical doses of genistein and 17β-estradiol, the main estrogen used in hormone replacement therapy in menopausal women. The present study evaluated the anxiolytic-like effects of identical doses of genistein and 17β-estradiol (0.045, 0.09, and 0.18 mg/kg/7 days, s.c.) in a surgical menopause model in rats in the elevated plus maze and locomotor activity tests at 12 weeks after ovariectomy. Additionally, the participation of estrogen receptor-βin the anxiolytic-like effect of genistein and 17β-estradiol was explored by previous administration of the 5 mg/kg tamoxifen antagonist. Genistein and 17β-estradiol (0.09 and 0.18 mg/kg) similarly reduced anxiety-like behavior in the elevated plus maze and also increased the time spent grooming and rearing, without affecting crossing in locomotor activity test. These effects were blocked by tamoxifen. Present results indicate that the phytoestrogen genistein has a similar behavioral profile as 17β-estradiol in rats at 12 weeks after ovariectomy through action at the estrogen receptor-β. Thus genistein has potential for reducing anxiety-like behavior associated with low concentrations of ovarian hormones, which normally occurs during natural and surgical menopause.

Zebrafish (Danio rerio) is a popular and valuable species used in many different biomedical research areas. The complex behavior that fish exhibit in response to different stimuli allows researchers to explore the biological and pharmacological basis of affective and mood disorders. In this sense, anxiety is commonly studied in preclinical research with animal models in rodents. During the last decade, those models have been successfully adapted to zebrafish. Stressful stimuli, such as novel environments, chemical substances, light conditions, and predator images, can trigger defensive behaviors considered indicators of an anxiety-like state. In the first stage, models were adapted and validated with different stressors and anxiolytic drugs with promising results and are now successfully used to generate scientific knowledge. In that sense, zebrafish allows several routes of administration and other methodological advantages to explore the anxiolytic effects of natural products in behavioral tests as novel tank, light-dark chamber, and black/white maze, among others. The present work will review the main findings on preclinical research using adult zebrafish to explore anxiolytics effects of natural products as plant secondary metabolites such as flavonoids, alkaloids and terpenes or standardized extracts of plants, among others. Scientific literature confirms the utility of zebrafish tests to explore anxiety-like states and anxiolytic-like effects of plant secondary metabolites, which represent a useful and ethical tool in the first stages of behavioral.

Pharmacotherapy for depression includes drugs such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), noradrenaline (NA) and serotonin (5-HT) reuptake inhibitors (NaSSAs), and atypical antidepressants; these drugs exert differentially beneficial effects on symptoms of depression after acute and chronic treatment in animal models. Said effects are established through neuroplastic mechanisms involving changes in neurogenesis and synaptogenesis as result of the activation of intracellular signaling pathways associated with neurochemical and behavioral changes. Antidepressants increase the synaptic availability of monoamines (monoaminergic hypothesis) such as 5-HT, NA, and gamma-aminobutyric acid (GABA) by inhibiting their reuptake or degradation and activating intracellular signaling pathways such as the responsive element binding protein (cAMP-CREB) cascade, which regulates the expression of genes related to neuroplasticity and neurogenesis, such as brain-derived neurotrophic factor (BDNF), in various brain structures implicated in depression. The aim of this review is to analyze the mechanisms of action of different antidepressants and to compare the effects of acute and chronic treatment on neuroplasticity in animal models of depression. A thorough search was conducted in PubMed, Scopus, and Web of Science, focusing on studies since 1996 with keywords like antidepressants, acute and chronic treatment, neuroplasticity, and experimental depression. Studies included had to investigate antidepressant effects experimentally, with full-text access, while excluding those that did not. Data extraction focused on study design, findings, and relevance to understanding treatment differences. Only high-quality, peer-reviewed studies were considered to ensure a comprehensive synthesis of current knowledge.