Molecular signature underlying (R)-ketamine rapid antidepressant response on anhedonic-like behavior induced by sustained exposure to stress.
Pharmacology, biochemistry, and behavior December 1, 2024 Ellen Scotton, Paola Rampelotto Ziani, Renata Luiza Boff Wilges et al. 1 citation
Anhedonia, a core symptom of major depressive disorder, was studied in male Wistar rats exposed to chronic variable stress. Rats classified as anhedonic-like showed reduced sucrose preference, which was reversed by a single dose of (R)-ketamine. High-throughput proteomics of the prefrontal cortex revealed that anhedonia was linked to downregulation of Neuronal Pentraxin Receptor and Galectin-1, suggesting disruption in inflammatory response, neurotransmitter activity, and glutamatergic synapses. (R)-ketamine response was associated with novel protein targets involved in oxidative stress, energy metabolism, synaptogenesis, dendritic arborization, neuroinflammation, gene expression, and telomere length. These pathways overlap with known depression pathophysiology and may offer therapeutic targets for anhedonia.