Affective biases shape cognitive and emotional behaviour and are important in major depressive disorder (MDD). Modulation of affective biases by the NMDA antagonist, ketamine, may underlie its antidepressant effects but not all NMDA antagonists are efficacious. Some studies suggest ketamine's efficacy involves non-NMDA mechanisms e.g. via its active metabolite HNK (2R, 6R)-hydroxynorketamine),...
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translational rodent model, we...
Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha–induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This suggests psilocybin can restore...
Abstract Background Behavioural studies in animal models represent a critical component of psychiatric drug development. Positive results in animal studies have identified novel therapeutic targets for major depressive disorder (MDD) but efficacy in humans has largely not been borne out in clinical trials. A possible reason for this failed translation is inappropriate dose selection and the...
Psychiatric disorders represent a particularly challenging area of medicine to study using non-human animals. They arise from a complex interaction between genetic and environmental factors and are diagnosed using clinical interviews and diagnostic criteria based largely on self-reported symptoms and with significant heterogeneity seen within patient populations. Anxiety and major depressive...
In recent years, public and academic interest into psychedelics has increased, given the clinical evidence of their potential benefits for treating psychiatric conditions such as major depressive disorder (MDD). While this has been accompanied by several landmark human studies, mechanistic studies in rodents are still relatively few, but such studies are crucial for understanding the...
Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent...
How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment....
Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients...
The biochemical targets for antidepressants are relatively well established, but we lack a clear understanding of how actions at these proteins translate to clinical benefits. This study used a novel rodent assay to investigate how different antidepressant drugs act to modify affective biases that have been implicated in depression. In this bowl-digging task, rats encounter two equal value...