Subthreshold doses of guanosine plus ketamine elicit antidepressant-like effect in a mouse model of depression induced by corticosterone: Role of GR/NF-κB/IDO-1 signaling.
A. Camargo, A. P. Dalmagro, Julia M. Rosa, Ana Lúcia B. Zeni, Manuella P. Kaster, C. Tasca, A. L. S. Rodrigues
Neurochemistry International July 8, 2020 DOI: 10.1016/j.neuint.2020.104797 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | CORT-induced mouse model of depression |
| Interventions | Ketamine Guanosine |
| Dose | 0.1 mg/kg ketamine i.p., 0.01 mg/kg guanosine p.o. |
| Duration | 21 days of CORT administration followed by single drug administration |
| Topics | Depression Esketamine Ketamine |
| Key points | A single coadministration of subthreshold ketamine and guanosine attenuated depressive-like behavior and hippocampal impairments in CORT-treated mice, with partial restoration of inflammatory and oxidative markers. |
Abstract
Augmentative treatment is considered the best second-option when a first-choice drug has partial limitations, particularly by allowing antidepressant dose reduction. Considering that ketamine has significant knock-on effects, this study investigated the effects of single coadministration with subthreshold doses of ketamine plus guanosine in a corticosterone (CORT)-induced animal model of depression and the role of anti-inflammatory and antioxidant pathways. CORT administration (20 mg/kg, p.o., for 21 days) increased the immobility time in the tail suspension test (TST) and the grooming latency in the splash test (SPT), as well as reduced the total time of grooming in the SPT. These behavioral alterations were accompanied by impaired hippocampal slices viability, elevated immunocontent of nuclear factor-kappa B (NF-κB) and indoleamine-2,3-dioxygenase 1 (IDO-1), and reduced immunocontent of glucocorticoids receptor (GR), glutamate transporter (GLT-1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in the hippocampus. CORT also decreased the thioredoxin reductase activity in the hippocampus, while reduced the glutathione reductase activity and non-protein thiols levels in both hippocampus and prefrontal cortex. In addition, elevated content of malondialdehyde and protein carbonyl was also observed in the hippocampus and prefrontal cortex of CORT-treated mice. Of note, a single administration of ketamine (0.1 mg/kg, i.p.) plus guanosine (0.01 mg/kg, p.o.) attenuated the depressive-like behavior and hippocampal slices impairments induced by CORT. The behavioral response obtained by the combined administration of these drugs was paralleled by the reestablishment of the CORT-induced molecular alterations on hippocampal GR, NF-κB, IDO-1, and GLT-1 immunocontent. Moreover, CORT-induced alterations on the antioxidant enzyme activity and oxidative stress markers were partially restored by ketamine plus guanosine treatment. Taken together, these findings suggest that guanosine might potentiate the effects of ketamine on inflammatory and oxidative markers that are elevated in depression.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.