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|
|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.
Our EEG platform has demonstrated robust differences in the sleep/wake profiles of Wistar Kyoto rats, (an endogenous model of depression) versus Sprague Dawley controls, which are also normalised by ketamine, and psilocybin treatment. Furthermore, the cognitive symptoms of depression, including working memory deficits, can also be modelled using WKY rats, with ketamine again demonstrating efficacy.
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 is a staple of the antidepressant screening catalogue. At Transpharmation we provide the FST in Sprague-Dawley or WKY rats.
- Elevated Zero MazeMice
- Open FieldMice
- Tail Suspension TestMice