Translational Neuropsychiatry Unit, Aarhus University, Denmark; Department of Nuclear Medicine and PET Center, Aarhus University and Hospital, Denmark.
2 papers in the library · 7 citations · publishing 2024-2025
In a rat model of depression (Flinders Sensitive Line), depressive behavior was negatively correlated with levels of the endocannabinoid 2-AG. A single dose of S-ketamine restored 2-AG levels and increased endocannabinoid signaling in the prefrontal cortex. Although S-ketamine decreased gene expression of the CB1 receptor and the enzyme FAAH, protein levels did not change significantly. S-ketamine increased CB1 receptor binding, and computer modeling suggested it may bind to CB1, CB2, GPR55, and FAAH. However, blocking CB1 receptors with rimonabant did not prevent S-ketamine's behavioral effects, indicating a complex interaction with the endocannabinoid system that requires further study.
Acute administration of S-ketamine, a fast-acting antidepressant, did not alter dopamine transporter (DAT) availability in the striatum of healthy female rats, as measured by [18F]FE-PE2I PET imaging and [3H]GBR-12935 autoradiography. This negative result suggests that changes in DAT binding are not involved in S-ketamine's rapid antidepressant mechanism, though further research is needed.