Modulation of the endocannabinoid system by (S)-ketamine in an animal model of depression.

Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.

Predictive utility of artificial intelligence on schizophrenia treatment outcomes: A systematic review and meta-analysis.

Identifying optimal treatment approaches for schizophrenia is challenging due to varying symptomatology and treatment responses. Artificial intelligence (AI) shows promise in predicting outcomes, prompting this systematic review and meta-analysis to evaluate various AI models' predictive utilities in schizophrenia treatment. A systematic search was conducted, and the risk of bias was evaluated.

Exploring the potential link between ΔFosB and -acetylcysteine in craving/relapse dynamics: can -acetylcysteine stand out as a possible treatment candidate?

From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that -acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.

All psychiatric disorders are equal, but some are more equal than others! An unconscious bias that calls for precision terminology.

We address the unconsciously biased perception of psychiatric disorders, highlighting a hierarchical perspective that favours certain diagnoses over others. We aim to uncover reasons for these inequities, emphasising the need for a shift toward pathophysiology-based nomenclature that can promote equal support for each disorder, enhance treatment adherence and encourage open discussions.

Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease: A focused review.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology.

Modulation of Leucine Sensors to Mitigate Antipsychotics-Induced Metabolic Syndrome: A New Vista.

Second-generation antipsychotics (SGAs) are currently the mainstay in the pharmacotherapy of some psychiatric disorders, which have improved the quality of life of millions of patients globally. A broad spectrum of activity and diminished liabilities of extrapyramidal side effects have made SGAs better alternatives compared to first-generation antipsychotics. Nevertheless, they display a complex profile of activity by affecting an array of biological targets and, as a result, are associated with a constellation of metabolic abnormalities such as hyperglycemia, dyslipidemia, weight gain, and cardiovascular problems.

Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders.

Estrogen receptors (ERs) play a multitude of roles in brain function and are implicated in various brain disorders. The use of positron emission tomography (PET) tracers for the visualization of ERs' intricate landscape has shown promise in oncology but remains limited in the context of brain disorders. Despite recent progress in the identification and development of more selective ligands for various ERs subtypes, further optimization is necessary to enable the reliable and efficient imaging of these receptors.

Sex and Estrous Cycle Are Not Mediators of S-Ketamine's Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression.

Background: Recent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine's antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach.

Rethinking treatment-resistant depression to quasi-tenacious depression.

With almost one-third of patients with major depression not adequately responsive to treatments, the management of treatment-resistant depression (TRD) has continued to be challenging. Recently, an essential step was taken to replace TRD with difficult-to-treat depression (DTD), pointing to some drawbacks associated with this terminology and identifying addressable barriers. In line with the DTD concept, we discuss why terming this population of patients as TRD could be semantically and clinically misleading.

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats.

Fatal opioid poisonings often involve methadone or morphine. This study aimed to elucidate if quetiapine, a widely used sedative antipsychotic medication, may increase the risk of fatal opioid poisoning by additive inhibitory effects on the central nervous system. We used data from 323 cases of fatal methadone or/and morphine poisonings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blinded placebo-controlled studies in 75 Flinders Resistant Line rats receiving three cumulative intraperitoneal doses of vehicle, methadone (2.

The intersection of astrocytes and the endocannabinoid system in the lateral habenula: on the fast-track to novel rapid-acting antidepressants.

Despite attaining significant advances toward better management of depressive disorders, we are still facing several setbacks. Developing rapid-acting antidepressants with sustained effects is an aspiration that requires thinking anew to explore possible novel targets. Recently, the lateral habenula (LHb), the brain's "anti-reward system", has been shown to go awry in depression in terms of various molecular and electrophysiological signatures.

Synaptic Vesicle Glycoprotein 2A: Features and Functions.

In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is involved in key functions of neurons, focused on the regulation of neurotransmitter release.

Tips and traps for behavioural animal experimentation.

Behavioural animal experimentation is an inseparable part of research trying to understand the biological underpinnings of human behaviour, diseases and disorders. Working with animals comes with great responsibility to achieve reliable and reproducible results of highest scientific quality. In a simple step-by-step fashion, we highlight some common issues that may occur along the path to conducting behavioural animal experimentations and posit some solutions and grounds to ensure the excellence of work done in this research area while aspiring to improve conditions for laboratory animals.

Comparing Copper Serum Level and Cognitive Functioning in Patients With Schizophrenia and Healthy Controls.

Introduction: The altered serum profiles of several trace elements have been reported in Schizophrenia (SCZ). This study was designed to elucidate whether the serum levels of Copper (Cu) and Magnesium (Mg), the two essential trace elements which contribute to neurotransmitter transmission, are altered in patients with SCZ. We also investigated whether there is an interrelation between cognitive functioning and the serum levels of Cu and Mg.

Looking into a Deluded Brain through a Neuroimaging Lens.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models.

When Thoughts Are in a Race: Area 10 and Bipolar Disorders.

Racing thought, when patients incessantly shift from one word or sentence to another while pending previous ones unfinished, is a symptom of (hypo)mania in bipolar disorders received less attention hitherto. Here, based on few evidence, we aim to unfold our hypothetical viewpoint that the frontopolar cortex that is believed to play a part in multitasking and management of competing goals might be dysfunctional in bipolar patients and may contribute in induction of flight of ideas. We then address new avenues for future research and try to encourage researchers to design more comprehensive studies to either accept or decline this proposed conjecture.

Validity and reliability of a Persian version of the Dissociative Experiences Scale II (DES-II) on Iranian patients diagnosed with schizophrenia and mood disorders.

Dissociative Experiences Scale (DES) is a valid self-reported tool to evaluate both non-pathological and pathological dissociative experiences. This study aims at evaluating the psychometric properties of a Persian version of the DES-II on both non-clinical samples and patients with schizophrenia and mood disorders. The back-translated DES-II was administered to 370 individuals being divided into three groups (270 healthy subjects, 50 patients with mood disorders, and 50 patients with schizophrenia) recruited from Shahid Beheshti Hospital of Kerman Medical University.

Bipolar disorder and the endocannabinoid system.

Objective: Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions.

Role of anxiety and depression in association with migraine and myofascial pain temporomandibular disorder.

Background: Previous studies have demonstrated a strong association between primary headaches (HAs) and temporomandibular disorders (TMDs), specifically the myofascial pain subtype of TMD (MP TMD). The role of anxiety and depression in presentation and maintenance of MP TMD and migraine is previously demonstrated. Therefore, the objective of the current study was to evaluate the modification effect of anxiety and depression on the possible association of MP TMD and migraine.

A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels.

Thrombosis is a shared perpetrating event in the pathophysiology of several cardiovascular disorders such as ischemic stroke, venous thromboembolism, atherosclerosis, and myocardial infarction. Despite holding a wide range of ammunition in our arsenal to ameliorate such conditions, we are still facing with many stumbling blocks in the satisfactory pharmacotherapy of cardiovascular diseases among which the risk of hemorrhage and life threatening drug interactions can be highlighted. Our hypothesis focuses on mimicking the nature of platelet activation, to design a novel targeted delivery system based on the alterations of a physical parameter, the hemodynamic shear stress, to aim at the offending thrombi in an attempt to offer a noninvasive, rapid, and monitoring-free method that not only can prolong the circulation time of the cargo, but also deliver it locally and reduce both the undesirable adverse effects and drug interactions.

Contribution of CB1Rs in anxiety-related behaviors but not locomotor deficits induced by methamphetamine.

Several lines of evidence have indicated that Methamphetamine (METH) exposure leads to neurodegenerative changes in the dopaminergic neurons and subsequently may predispose users to motor deficit. On the other hand, there is a reciprocal regulation between the endocannabinoid and the dopaminergic systems. Previous studies also showed that the endocannabinoids are involved in the signaling mechanisms of various brain regions related to motor and cognitive functions.

Attenuation Effect of Cannabinoid Type 1 Receptor Activation on Methamphetamine-Induced Neurodegeneration and Locomotion Impairments among Male Rats.

Background: A number of neuroimaging studies on human addicts have revealed that abuse of Methamphetamine (METH) can induce neurodegenerative changes in various brain regions like the cerebral cortex and cerebellum. Although the underlying mechanisms of METH-induced neurotoxicity have been studied, the cellular and molecular mechanisms of METH-induced neurotoxicity remain to be clarified. Previous studies implicated that cannabinoid type 1 receptors (CB1Rs) exert neuroprotective effects on several models of cerebral toxicity, but their role in METH-induced neurotoxicity has been rarely investigated.

Modulation of sphingosine-1-phosphate receptor ameliorates harmaline-induced essential tremor in rat.

Essential tremor (ET) is one of the most common movement disorders with unknown etiology. Despite lack of effective clinical treatments, some potential therapeutic factors and modulation of some neurotransmitters have been utilized to ameliorate motor symptoms in the animal models of tremor. In the current study, male Wistar rats (n=10 in each group) weighing 40-60g were divided into vehicle control groups (saline or DMSO), saline/DMSO+harmaline (30mg/kg, i.

A Brain on a Roller Coaster: Can the Dopamine Reward System Act as a Protagonist to Subdue the Ups and Downs of Bipolar Disorder?

One of the most interesting but tenebrous parts of the bipolar disorder (BD) story is the switch between (hypo)mania and depression, which can give bipolar patients a thrilling, but somewhat perilous, 'ride'. Numerous studies have pointed out that there are some recognizable differences (either state-dependent or state-independent) in several brain regions of people with BD, including components of the brain's reward system. Understanding the underpinning mechanisms of high and low mood statuses in BD has potential, not only for the development of highly specific and selective pharmaceutical agents, but also for better treatment approaches and psychological interventions to manage BD and, thus, give patients a safer ride.