Summary: Ketamine is a rapid action antidepressant which can relieve the symptoms of the major depressive disorder (MDD) in a few hours, even in cases resistant to treatment. However, its effects generally only last a week, and the frequent dosage has risks such as dissociation or dependence.
A new study shows that the advantages of ketamine can be extended up to two months using a compound that improves ERK signaling, an essential long -term path of Ketamine. This breakthrough provides proof of principle for safer and more sustained depression treatment strategies targeting intracellular mechanisms.
Key facts:
- Quick action relief: Ketamine reduces depression symptoms in a few hours, even in resistant patients.
- Prolonged efficiency: A compound called BCI has extended the antidepressant effect of ketamine for up to two months.
- Mechanism -based strategy: Improving ERK signaling can help maintain antidepressant effects from a single dose.
Source: Vanderbilt University
About 10% of the American population is afflicted by a major depressive disorder at any time, and up to 20% will present symptoms of private label during their lifetime.
However, despite its prevalence, CT treatment methods are often below a non -insignificant part of the population. Antidepressants – The treatment standard – do not work for 30% with the private label.
When infused at a low -dose dose, ketamine shows remarkable effectiveness such as a rapid action antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments.
However, coherent infusions of ketamine are necessary to maintain the symptoms remotely, which could cause side effects, such as dissociative behaviors and the possibility of dependence, and stopping treatment can cause relapse.
In a new study published in ScienceLisa Montegia and Ege Kavalali’s laboratories show that it is possible to considerably extend the efficiency of a single dose of ketamine from its current duration of up to a longer period of up to two months.
“The premise of this study, led by Zhenzhong MA, a fantastic deputy research teacher, was based on a testable mechanistic model that we have developed who explains the rapid antidepressive action of Ketamine,” said Montegia.
Montegia holds the Lee E. Limbird pulpit in pharmacology and is the director of the Barlow family of the Vanderbilt Brain Institute.
Previously, researchers in the field had determined that the antidepressant effect of ketamine requires the activation of a key signaling route called ERK, but only the long -term effects of ketamine – not its rapid effects – are deleted when Erk is inhibited.
As an antidepressant with rapid action, ketamine is based on synaptic plasticity dependent on ERK to produce its rapid behavioral effects. MA and his colleagues hypothesized that they could maintain the effects of ketamine for longer periods by improving the ERK activity.
In the recent article, I discovered that the antidepressant effects of ketamine could be maintained up to two months using a drug called BCI, which inhibits a protein phosphatase and causes an increase in ERK activity.
By inhibiting phosphatase, the authors have retained ERK’s activity and increased synaptic plasticity which causes prolonged antidepressant effects of ketamine.
Although the use of BCI makes it difficult to apply these results to the clinic, Montegia said that the results provide proof in principle that the antidepressive action of ketamine can be maintained by targeting intracellular signaling.
She and Kavalali, the experimental therapy professor of William Stokes and president of the Department of Pharmacology, have worked on the project since its creation and hope that it promotes other studies which seek to identify specific molecules which will improve and support the action of a single dose of ketamine.
In the end, this work will be a springboard towards improving the life of TDM patients by reducing the burden of treatment.
About this news of the research of psychopharmacology and depression
Author: Marissa Shapiro
Source: Vanderbilt University
Contact: Marissa Shapiro – Vanderbilt University
Picture: The image is credited with Neuroscience News
Original search: Closed access.
“Improved ERK activity extends the antidepressant effects of ketamine by increasing synaptic plasticity” by Lisa Montegia et al. Science
Abstract
Improved ERK activity extends the antidepressant effects of ketamine by increasing synaptic plasticity
Repeated treatment of ketamine to maintain a rapid antidepressant effect can cause side effects over time, highlighting an unwatering clinical need to maintain the antidepressive action of this medication from a single administration.
It was proposed that the synaptic potentization induced by ketamine at CA3-CA1 synapses, a key synaptic substrate for antidepressing action.
Here, we found that the Synaptic Potentization CA3-CA1 induced by ketamine could be increased by increasing the extracellular kinase activity regulated by extracellular signal (ERK) by pharmacological inhibition of phosphatases with double specificity 6 (DUSP6).
The behavioral effects of the antidepressant type of the acute treatment of ketamine have been extended by inhibition of DUSP6 up to 2 months.
The selective deletion of tropomyosin kinase B (TRKB) in excitatory neurons abolished these synaptic and behavioral effects mediated by Dusp6 inhibition.
These data suggest that the rapid antidepressant effects of ketamine can be maintained by selectively targeting intracellular signaling downstream.
