Depression and the Glutamate/GABA-Glutamine Cycle.
Current neuropharmacology January 1, 2024 Mortimer Mamelak 24 citations
Rodent models of psychological stress mirror many features of major depressive disorder, linking activation of the hypothalamic-pituitary axis to oxidative stress, neuroinflammation, dominance of cholinergic neurotransmission, increased REM sleep pressure, impaired glycolysis and brain glucose utilization, reduced energy production, and decreased glutamate/GABA-glutamine cycling. Rapidly acting antidepressants like scopolamine, ketamine, and ECT raise extracellular glutamate; scopolamine and ketamine increase glutamate/GABA-glutamine cycling in both men and rodents, providing short-term relief. Nightly use of gammahydroxybutyrate (GHB), a GABAB agonist, may achieve more permanent results and possibly prevent depression by inhibiting cholinergic neurotransmission, relieving REM sleep pressure, and generating NADPH and succinate to boost energy and glutamate synthesis.