Low doses of ketamine and guanosine abrogate corticosterone-induced anxiety-related behavior, but not disturbances in the hippocampal NLRP3 inflammasome pathway
| Autor: | Daiane B. Fraga, Julia M. Rosa, Manuella P. Kaster, Ana Lúcia S. Rodrigues, Ana Lúcia Bertarello Zeni, Anderson Camargo, Ana Paula Dalmagro |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Psychopharmacology. 238:2555-2568 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-021-05879-8 |
| Popis: | Guanosine has been shown to potentiate ketamine’s antidepressant-like actions, although its ability to augment the anxiolytic effect of ketamine remains to be determined. This study investigated the anxiolytic-like effects of a single administration with low doses of ketamine and/or guanosine in mice subjected to chronic administration of corticosterone and the role of NLRP3-driven signaling. Corticosterone (20 mg/kg, p.o.) was administered for 21 days, followed by a single administration of ketamine (0.1 mg/kg, i.p.), guanosine (0.01 mg/kg, p.o.), or ketamine (0.1 mg/kg, i.p.) plus guanosine (0.01 mg/kg, p.o.). Anxiety-like behavior and NLRP3-related targets were analyzed 24 h following treatments. Corticosterone reduced the time spent in the open arms and the central zone in the elevated plus-maze test and open-field test, respectively. Corticosterone raised the number of unsupported rearings and the number and time of grooming, and decreased the latency to start grooming in the open-field test. Disturbances in regional distribution (increased rostral grooming) and grooming transitions (increased aborted and total incorrect transitions) were detected in corticosterone-treated mice. These behavioral alterations were accompanied by increased immunocontent of Iba-1, ASC, NLRP3, caspase-1, TXNIP, and IL-1β in the hippocampus, but not in the prefrontal cortex. The treatments with ketamine, guanosine, and ketamine plus guanosine were effective to counteract corticosterone-induced anxiety-like phenotype, but not disturbances in the hippocampal NLRP3 pathway. Our study provides novel evidence that low doses of ketamine and/or guanosine reverse corticosterone-induced anxiety-like behavior and shows that the NLRP3 inflammasome pathway is likely unrelated to this response. |
| Databáze: | OpenAIRE |
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