Depression / Anxiety
It is estimated that over 300 million people globally suffer from depression. Selective Serotonin Reuptake Inhibitors (SSRIs) have been on the market since the late 1980s and still represent an invaluable pharmacological intervention in depression. However, 30-40% of patients do not respond to treatment - a subpopulation defined as Treatment Resistant Depression (TRD). The discovery that low doses of the anaesthetic and recreational drug ketamine has rapid and long-lasting antidepressant effects in TRD is opening a new era for drug discovery in depression.
Transpharmation has developed a platform of sensitive and highly consistent pharmacodynamic screening assays responsive to standard SSRIs, anxiolytics, and most recently ketamine and psilocybin:
|Anxiety-related:||Elevated Zero Maze, Open Field, Light/Dark Box, Novelty Suppressed Feeding Test, Light-Dark Dark Challenge Assay with Thigmotaxis|
|Depression-related:||Forced Swim Test, Tail Suspension Test|
We aim to deliver highly translational models with high construct, face and predictive validity, sensitive to the effects of NCSs, providing a potential means to investigate the basic neuropathology underlying affective illnesses such as anxiety, depression and TRD.
Our scientific portfolio includes:
- When considering experimental approaches to study depression, social interaction based CSD paradigm, has been considered a highly translational model due to its etiological validity. Following 10 days of social defeat, groups of C57BL/J6 mice that are resilient and susceptible to chronic stress can be distinguished. Social aversion can be reversed by the chronic but not acute SSRI treatment and acute ketamine treatment. Additional behavioural end points enable depression and anxiety-related observations.
- Discover the power of EEG recording as a valuable, translational tool for characterization of sleep, mood disorders, and more. Since similar EEG readouts can be made from both rodents and human patients, EEG serves as a highly translational tool in preclinical drug discovery. Many currently marketed drugs have clear dose and time-dependent effects on specific EEG frequency bands, which can serve as pharmacodynamic biomarkers for target engagement, efficacy and tolerability. Our services include studying potential antidepressants' and sleep modulators' effects on rodents EEG through novel DSI technology of wireless bipotential telemetry. Transpharmation's recent findings demonstrate the effect of sleep-inducing zolpidem (10 & 30 mg/kg) and anti narcoleptic modafinil (100 & 300 mg/kg) as well as ketamine (5 & 10 mg/kg) and psilocybin (3 & 10 mg/kg) on sleep and EEG in male C57BL/6 mice.
- The progressive ratio task is a translational operant behavioural task used to objectively measure effort-based motivation. The task is used in clinical populations and has demonstrated that people with depression exhibit deficits in responding to rewards with increasing levels of effort. Similarly in preclinical testing, chronic stress models of depression and administration of tetrabenazine have shown reduced responding of rats in the task. At Transpharmation we provide this task with several pharmacological interventions demonstrating either an increase or decrease in performance based on your needs to test your compounds against.
- The Forced Swim Test (FST) is a rodent behavioural test used to evaluate “depressive-like” states and behavioural despair. It is also a widely accepted method used to assess stress coping ability in mice, where the administration of a wide range of antidepressants increases the animal's active movement time. It has been found that exposure to the FST can cause neurochemical changes consistent with a depressive phenotype. For example, serotonin and norepinephrine levels in cortical and limbic structures may temporarily decrease. The forced swim test is a staple of the antidepressant screening catalogue. At Transpharmation we provide the FST in Sprague-Dawley or WKY rats.
- The Elevated Zero Maze (EZM) is a widely used test to assess anxiety-like behavior in rodents, which is based on their conflicting innate tendencies: exploring a new environment and avoiding elevated and open spaces. The EZM test, which is a modification of the Elevated Plus Maze (EPM) test, offers increased motivation for animals to explore the open and brightened areas, due to the more continuous nature of the apparatus and the absence of the central square. The EZM test demonstrates high predictive validity in assessing the effectiveness of anxiolytic agents, resulting in an increased time spent by animal in the open arms.
- The open field test is used to assess overall level of motor activity, anxiety-like behaviour and willingness to explore new areas by laboratory animals. While mice have a natural aversion to brightly lit and, open spaces, they also desire to explore new environments. Administration of substances with anti-anxiety effect, such as buspirone (0.3 mg/kg i.p.), leads to increased exploratory behaviour.
- The tail suspension test serves as a valuable tool in the area of drug discovery, facilitating high-throughput screening of prospective antidepressant compounds. The test is based on the observation that mice develop an immobile posture while suspended by their tails with tape, in a position where it cannot escape or hold on to nearby surfaces. Administration of substances with an antidepressant effect, such as imipramine (10 mg/kg i.p.), result in mice exhibiting an extended time of active movement.
- The Novelty Suppressed Feeding test (NSF), which is based on hyponeophagia (a phenomenon where exposure to a novel environment suppresses feeding behavior), has been used extensively to assess anxiety-related behavior in mice. Validated by our research team, the NSF test is an effective behavioral paradigm for evaluating the efficacy of treatments with drugs such as anxiolytics and antidepressants, as their administration result in a decrease in the time (latency) needed by animal to initiate feeding in the novel, anxiogenic environment.
- This multifaceted assay is pivotal for gauging the impact of potential anxiolytic compounds, providing a holistic view of zebrafish behavioural patterns. The assay evaluates the anxiety-like behaviour in zebrafish in a two-fold approach: first, measuring activity in response to light changes, and second, focusing on the zebrafish's inherent tendency to stay close to walls or boundaries through thigmotaxis. Our research suggests that 10 μM diazepam demonstrates prominent anxiolytic effects.