Ketamine, a drug that blocks NMDA receptors, produces rapid antidepressant-like effects in male mice, reducing immobility in a forced swimming test. At a high dose (10 mg/kg), it increased dopamine and serotonin levels in the striatum, along with dopamine metabolites DOPAC and HVA. These changes were linked to increased tyrosine hydroxylase and decreased dopamine and serotonin transporter immunoreactivities in the striatum and hippocampus. The findings suggest ketamine's antidepressant action involves enhancement of monoamine pathways, particularly by raising dopamine and serotonin availability through effects on their synthesizing enzyme and transporters.
A single oral dose of ibogaine (20 mg/kg) in female Wistar rats caused transient oxidative stress in the brain and depleted glycogen stores in the liver. Six hours after treatment, lipid peroxidation (TBARS) increased significantly, while after 24 hours it returned to control levels. Protein free sulfhydryl groups increased, but nonprotein free sulfhydryl groups (indicating reduced glutathione) decreased, both more pronounced at 24 hours. Despite these signs of oxidative stress, the activities of antioxidative enzymes (SOD, CAT, GSH-Px, GR) and glutathione S-transferases remained unchanged. Liver glycogen was reduced, more at 6 hours than at 24 hours, suggesting a transient depletion of energy reserves that begins to recover within a day. These findings suggest ibogaine induces rapid, reversible changes in redox and energy homeostasis.