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Journal of Neuroscience Research Jul 2022The lateral septum (LS) is a structure in the midline of the brain that is interconnected with areas associated with stress and feeding. This review highlights the role... (Review)
Review
The lateral septum (LS) is a structure in the midline of the brain that is interconnected with areas associated with stress and feeding. This review highlights the role of the LS in anxiety, depression, and eating disorders and their comorbidity. There is a prevailing view that the LS is anxiolytic. This review finds that the LS is both anxiolytic and anxiogenic. Furthermore, the LS can promote and inhibit feeding. Given these shared roles, the LS represents a common site for the comorbidity of neuropsychiatric disorders, and therefore a potential pharmacological target. This is crucial since currently available treatments are not always effective. Corticotrophin-releasing factor 2 antagonists are potential drugs for the treatment of anxiety and anorexia and require further research. Furthermore, other drugs currently in trials for binge eating, such as alpha-adrenergic agonists, may in fact promote food intake. It is hoped that the advancements in chemo- and optogenetic techniques will allow future studies to profile the specific neural connections of the LS and their function. This information could facilitate our understanding of the underlying mechanisms, and therefore pharmacological targets, of these psychiatric conditions.
Topics: Anti-Anxiety Agents; Anxiety; Optogenetics
PubMed: 35443088
DOI: 10.1002/jnr.25052 -
Physiology & Behavior Nov 2023Anxiety disorders pose a significant challenge in contemporary society, and their impact in terms of social and economic burden is overwhelming. Behavioral research... (Review)
Review
Anxiety disorders pose a significant challenge in contemporary society, and their impact in terms of social and economic burden is overwhelming. Behavioral research conducted on animal subjects is crucial for comprehending these disorders and, from a translational standpoint, for introducing innovative therapeutic approaches. In this context, the Hole-Board apparatus has emerged as a widely utilized test for studying anxiety-related behaviors in rodents. Although a substantial body of literature underscores the utility and reliability of the Hole-Board in anxiety research, recent decades have witnessed a range of studies that have led to uncertainties and misinterpretations regarding the validity of this behavioral assay. The objective of this review is twofold: firstly, to underscore the utility and reliability of the Hole-Board assay, and concurrently, to examine the underlying factors contributing to potential misconceptions surrounding its utilization in the study of anxiety and anxiety-related behaviors. We will present results from both conventional quantitative analyses and multivariate approaches, while referencing a comprehensive collection of studies conducted using the Hole-Board.
Topics: Humans; Animals; Reproducibility of Results; Behavior, Animal; Anxiety; Anti-Anxiety Agents; Anxiety Disorders; Exploratory Behavior
PubMed: 37690695
DOI: 10.1016/j.physbeh.2023.114346 -
Progress in Neuro-psychopharmacology &... Apr 2023Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in...
Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice.
Topics: Animals; Mice; Anti-Anxiety Agents; Anxiety; Astrocytes; Brain; Disease Models, Animal; Hippocampus; Sirtuins; Stress, Psychological
PubMed: 36565979
DOI: 10.1016/j.pnpbp.2022.110702 -
Steroids Aug 2022Mifepristone is a non-selective progesterone (PR), glucocorticoid (GR), and androgen receptor (AR) antagonist with antidepressant and anxiolytic effects. The dose and... (Review)
Review
Mifepristone is a non-selective progesterone (PR), glucocorticoid (GR), and androgen receptor (AR) antagonist with antidepressant and anxiolytic effects. The dose and duration of mifepristone administration vary in rodent preclinical studies to evaluate depression-like and anxiety-like behavior. This review summarizes the findings so far and attempts to reconcile some of the differences in the results. While a few studies assessed basal depression- and anxiety-like behavior, several studies have used mifepristone in conjunction with stress, corticosterone/dexamethasone (after adrenalectomy), or progesterone administration. The effect of mifepristone on depression-like behavior appears to depend not only on the dose and duration of administration but also on the intensity or type of stress. In addition, the anxiolytic effects may depend on the species and strain of the experimental animals. More reports assess antidepressant-like or anxiolytic-like effects following acute than chronic administration. These effects are dependent on the paradigms and the nature of stressors. Most mifepristone studies implicate the role of GRs, yet only two reports have confirmed its role using a genetic approach, whereas none implicate the role of PRs/ARs. There are several novel selective GR antagonists whose effects on depression- and anxiety-like behavior are yet to be studied. Future studies could aim to confirm the role of GRs and evaluate the contribution of PRs/ARs to the effects of mifepristone. Such studies will contribute to a better understanding of depression, anxiety, and other mood disorders and develop novel strategies, particularly for treatment-resistant conditions.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Depression; Glucocorticoids; Mifepristone; Progesterone; Receptors, Glucocorticoid; Rodentia
PubMed: 35679911
DOI: 10.1016/j.steroids.2022.109058 -
Molecular Psychiatry Jan 2022Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade,... (Review)
Review
Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.
Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Psychiatry; Psychometrics
PubMed: 34561614
DOI: 10.1038/s41380-021-01299-4 -
Pharmacology, Biochemistry, and Behavior Sep 2022Pharmacological modulation of glutamate has long been considered to be of immense therapeutic utility. The metabotropic glutamate receptors (mGluRs) are potential... (Review)
Review
Pharmacological modulation of glutamate has long been considered to be of immense therapeutic utility. The metabotropic glutamate receptors (mGluRs) are potential targets for safely altering glutamate-driven excitation. Data support the potential therapeutic use of mGluR modulators in the treatment of anxiety, depression, schizophrenia, and other psychiatric disorders, pain, epilepsy, as well as neurodegenerative and neurodevelopmental disorders. For each of the three mGluR groups, compounds have been constructed that produce either potentiation or functional blockade. PET ligands for mGlu5Rs have been studied in a range of patient populations and several mGlu5R antagonists have been tested for potential efficacy in patients including mavoglurant, diploglurant, basimglurant, GET 73, and ADX10059. Efficacy with mGlu5R antagonists has been reported in trials with patients with gastroesophageal reflux disease; data from patients with Parkinson's disease or Fragile X syndrome have not been as robust as hoped. Fenobam was approved for use as an anxiolytic prior to its recognition as an mGlu5R antagonist. mGlu2/3R agonists (pomaglumated methionil) and mGlu2R agonists (JNJ-40411813, AZD 8529, and LY2979165) have been studied in patients with schizophrenia with promising but mixed results. Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression. The Group III mGluRs are the least developed of the mGluR receptor targets. The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders.
Topics: Anti-Anxiety Agents; Glutamates; Humans; Parkinson Disease; Receptors, Metabotropic Glutamate; Schizophrenia
PubMed: 35987339
DOI: 10.1016/j.pbb.2022.173446 -
Pharmacological Research Jul 2021The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAR), and the down-regulation of its... (Review)
Review
The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAR), and the down-regulation of its biosynthesis have been attributed to the development of mood disorders, such as depression, anxiety and post-traumatic stress disorder (PTSD). ALLO mediated depression/anxiety involves GABAergic mechanisms and appears to be related to brain-derived neurotrophic factor (BDNF), dopamine receptor, glutamate neurotransmission, and Ca channel. In the clinical, brexanolone, as a newly developed intravenous ALLO preparation, has been approved for the treatment of postpartum depression (PPD). In addition, traditional antidepressants such as selective serotonin reuptake inhibitor (SSRI) could reverse ALLO decline. Recently, the translocation protein (TSPO, 18 kDa), which involves in the speed-limiting step of ALLO synthesis, and ALLO derivatization have been identified as new directions for antidepressant therapy. This review provides an overview of ALLO researches in animal model and patients, discusses its role in the development and treatment of depression/anxiety, and directs its therapeutic potential in future.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Depression; Humans; Mood Disorders; Pregnanolone; Receptors, GABA-A
PubMed: 34019980
DOI: 10.1016/j.phrs.2021.105682 -
Central Nervous System Agents in... 2023is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. is used as...
BACKGROUND
is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. is used as a brain tonic. The plant is reported to be a prominent memory-improving drug. It is used as a psychostimulant and tranquilizer. It is reported to reduce mental tension.
OBJECTIVE
The present study aimed to explore the protective effect of hydroalcoholic extract from the leaves of along with CNS depressant and anti-anxiety activities, in models of mice.
METHODS
The extract from leaves of were sequentially isolated with a mixture of water and alcohol solution in the soxhlet apparatus. An acute toxicity study was conducted as per OECD guidelines no. 423, in which 18 Albino male mice were treated with different doses (1, 10, 100, 500, 1000, and 2000 mg/kg) of hydroalcoholic extract of and assessed for toxicity parameters for 14 days. Various psychomotor activities of hydroalcoholic extract from leaves of for 100, 200, and 300 mg/kg doses were performed in mice by using various tests like actophotometer, open field, rota-rod, grip strength tests, elevated plus maze, hole board test, inclined plane, chimney test.
RESULTS
The hydroalcoholic extract from leaves of was found to fall under category 4 in the acute toxicity study. Therefore, 100, 200, and 300 mg/kg doses of hydroalcoholic extract of leaves of were selected for the further pharmacological study. The results of psychomotor tests (actophotometer, open field, rota-rod, grip strength, hole board test, inclined plane, chimney test, elevated plus maze, light-dark model) for test doses 100, 200, and 300 in mice showed CNS depressant and anti-anxiety effects.
CONCLUSION
Hydroalcoholic extract from leaves of at the 100, 200, and 300 mg/kg doses has shown CNS depressant and anti-anxiety effects in mice models.
Topics: Mice; Animals; Convolvulus; Plant Extracts; Anti-Anxiety Agents; Central Nervous System Depressants; Plant Leaves
PubMed: 36825716
DOI: 10.2174/1871524923666230220144640 -
The Journal of Maternal-fetal &... Dec 2023While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large...
While medications for anxiety and depression are commonly used in the United States, it is unclear to what degree they are continued during pregnancy. We used a large administrative database to determine whether psychiatric medications are continued during pregnancy and predictors of continued medication treatment. Of 2,672,656 women included in our analysis, 86,454 (3.1%) filled a pre-pregnancy prescription for an anxiolytic or antidepressant medication within 3 months of estimated conception. Of women who filled a pre-pregnancy prescription, 49.4%, 26.1%, and 20.1% filled subsequent prescriptions in the 1st, 2nd, and 3rd trimesters. Discontinuation rates ranged by pharmaceutical agent, from 16% for fluoxetine to 71% for alprazolam. White women and women over 25 were more likely to continue anxiolytic and antidepressant treatment during pregnancy. Because untreated and under-treated mental health conditions are linked to adverse maternal outcomes, high discontinuation rates may have important implications for maternal health.
Topics: Pregnancy; Female; Humans; United States; Depression; Anti-Anxiety Agents; Antidepressive Agents; Fluoxetine; Pharmaceutical Preparations; Pregnancy Complications
PubMed: 36710395
DOI: 10.1080/14767058.2023.2171288 -
Acta Gastro-enterologica Belgica 2023Functional dyspepsia is a common chronic condition with upper abdominal symptoms in the absence of an organic cause. The first line treatment consists of protonpomp... (Review)
Review
BACKGROUND AND STUDY AIMS
Functional dyspepsia is a common chronic condition with upper abdominal symptoms in the absence of an organic cause. The first line treatment consists of protonpomp inhibition or Helicobacter pylori eradication. However, this approach often does not provide enough symptom relief. Neuromodulating agents are commonly used in clinical practice but only tricyclic antidepressant (TCAs) are mentioned in European and American and Canadian guidelines.
METHODS
We performed a comprehensive review of the literature in Pubmed for full-text randomized controlled trials in English with adult participants (>18 years) who met the Rome II, III or IV criteria or were diagnosed by a physician with a negative upper endoscopy and that compared a neuromodulating agent with placebo.
RESULTS
The search strategy identified 386 articles of which 14 articles met the eligibility criteria. TCAs like amitriptyline and imipramine have been shown to be effective in the treatment of functional dyspepsia whereas other neuromodulating agents like tetracyclic antidepressants, levosulpiride and anxiolytics might be beneficial but conclusive evidence is lacking. serotonin and noradrenaline reuptake inhibitors (SNRI) and selective serotonin reuptake inhibitors (SSRI) have not shown benefit in patients with functional dyspepsia.
CONCLUSION
Selected neuromodulators have an established efficacy in functional dyspepsia. The best supporting evidence is available for TCAs with a potential role for tetracyclic antidepressants, levosulpiride and anxiolytics.
Topics: Adult; Humans; Anti-Anxiety Agents; Antidepressive Agents; Antidepressive Agents, Tricyclic; Canada; Dyspepsia; Selective Serotonin Reuptake Inhibitors; Randomized Controlled Trials as Topic
PubMed: 36842175
DOI: 10.51821/86.1.10998