A single subanesthetic dose of ketamine (10 mg/kg) reduced depressive-like behavior and oxidative stress in a rodent model of treatment-resistant depression induced by adrenocorticotropic hormone (ACTH). ACTH increased superoxide anion, advanced oxidation protein products, malondialdehyde, and total oxidant status, while decreasing superoxide dismutase and paraoxonase1 activity and increasing DNA damage in peripheral blood lymphocytes. Ketamine reversed these effects, lowering oxidative markers and enhancing antioxidant enzyme activity. The findings suggest ketamine's antidepressant action may involve antioxidant mechanisms, supporting further clinical research on its effects on reactive oxygen species metabolism and antioxidant defenses in depression.
The brain's ability to reorganize itself, known as neuroplasticity, is now understood to be more flexible and treatable in adults than previously believed. This review examines drugs that target key synaptic receptors (NMDA, AMPA, GABA), neuropeptide systems (BDNF, oxytocin, vasopressin), and psychedelic compounds (psilocybin, LSD, ketamine). Evidence shows that NMDA antagonists produce rapid antidepressant effects, classic psychedelics reorganize brain structure and function through 5-HT2A receptor activation, and neuropeptides support synaptic repair. The authors emphasize safety concerns, risks of harmful plasticity, and the need for controlled dosing and patient selection. Emerging non-hallucinogenic neuroplastogens and combination therapies may offer safer ways to enhance plasticity for treating neuropsychiatric and neurodegenerative disorders.
Ketamine infused into the nucleus accumbens (NAc) reduces fear generalization in mice, a core symptom of post-traumatic stress disorder. Foot shock strength-dependently induced fear generalization, increasing c-fos activity, lowering GluR1(S845) and GluR1(S831) protein levels, and raising P-GluN2B protein in the NAc. Local ketamine infusion decreased fear generalization while increasing GluR1(S845) and GluR1(S831) and decreasing P-GluN2B. The findings suggest ketamine may attenuate fear generalization by affecting glutamatergic signaling in the NAc.