January 8, 2014
Promising Antidepressant Ketamine Works By Giving Quick Seratonin Boost, Says New Study
Rebekah Eliason for redOrbit.com – Your Universe Online
A new study revealed that the drug ketamine, a potent anesthetic used in human and veterinary medicine and as an illegal recreational drug, is a potential candidate for fast treatment of depression for individuals who do not respond to other types of medications.
From the RIKEN Center for Life Science Technologies in Japan, new research using PET imaging studies has demonstrated that ketamine increases the activity level of serotonergic neurons in brain areas that regulate motivation in macaque monkeys. Researchers concluded that the effects of ketamine on serotonin, often referred to as the 'feel-good neurotransmitter,' could provide an explanation for its effects as an antidepressant in humans.
This new study utilizes Positron Emission Tomography (PET) molecular imaging and demonstrates that this technique may be a useful in diagnosing major depressive disorder in humans and in developing new antidepressants.
Recently, ketamine was found to act as an antidepressant with short onset and long-term duration among patients suffering from treatment-resistant major depressive disorder. The typical treatment for major depressive disorder includes selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors and tricyclic antidepressants.
The mechanism behind ketamine’s effect on the depressive brain is still unclear. In this study, Dr. Hajime Yamanaka and Dr. Hirotaka Onoe designed a PET imaging method on conscious non-human primates to understand the effects of ketamine on the serotonergic system in the brain. Along with an international team, they performed the PET study on rhesus monkeys.
The researchers performed a PET imaging study on four rhesus monkeys. Two types of molecules known as tracer molecules were used because they bind almost exclusively to the serotonin 1B receptor 5-HT1B and the serotonin transporter.
Analysis of the images generated by the PET scans enabled the researchers to determine that ketamine causes increased binding of serotonin to its receptor 5-HT1B in the nucleus accumbens and ventral pallidum. It also causes decreased binding to the transporter SERT in the same brain regions. Both the nucleus accumbens and ventral pallidum are brain regions which are associated with motivation and are closely related to depression.
Additionally, the researchers discovered that using the drug NBQX, which is known to obstruct the antidepressive effects of ketamine in rodents, cancels the effect of ketamine on the serotonin receptor but not on the SERT transporter.
Combining this information, researchers were able to determine the mechanism for ketamine is possibly caused by an increase in the expression of receptors that is mediated by the glutamate AMPA receptor.
The team's study was published this week in the journal Translational Psychiatry.