Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats.
Lêda S B Garcia, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Laura Stertz, Flávio Kapczinski, Elaine C Gavioli, João Quevedo
Progress in neuro-psychopharmacology & biological psychiatry April 30, 2009 DOI: 10.1016/j.pnpbp.2009.01.004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Rats exposed to chronic mild stress |
| Intervention | Ketamine |
| Dose | 15 mg/kg |
| Duration | 40 days of CMS, then acute or chronic treatment |
| Measures | sweet food consumption, body weight, adrenal gland weight, corticosterone levels, ACTH levels, hippocampal BDNF protein levels |
| Topics | Esketamine Ketamine |
| Key findings | Chronic mild stress induced anhedonia, adrenal hypertrophy, reduced weight gain, and elevated corticosterone and ACTH. Acute and chronic ketamine reversed adrenal and hormonal changes and restored weight, but only repeated ketamine reversed anhedonia. Ketamine did not affect hippocampal BDNF in stressed rats. |
Abstract
Several studies have supported the idea that ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) is an important player in the etiology of psychopathologies, such as anxiety disorders and major depression. Additionally, studies have shown that ketamine induces antidepressant effects in humans as well as in rodents subjected to animal models of depression. In this context, the present study was aimed to evaluate behavioral and physiological effects of acute and chronic administration of ketamine, a NMDA receptor antagonist, in rats exposed to chronic mild stress (CMS). After 40 days of CMS, rats were treated with ketamine (15 mg/kg) and sweet food consumption, body and adrenal gland weight, corticosterone and adrenocorticotropic (ACTH) hormone levels, and hippocampal BDNF protein levels were assessed. Our findings demonstrated that CMS evoked anhedonia, induced hypertrophy of adrenal gland, impaired gain of body weight and increased corticosterone and ACTH circulating levels in rats. Acute and chronic treatment with ketamine reversed the increase in adrenal gland weight, promoted regain of body weight, and normalized corticosterone and ACTH circulating levels. Repeated, but not acute, administration of ketamine reversed anhedonia-like behavior, although the treatment with ketamine per se increased sweet food consumption in non-stressed rats. Finally, acute and chronic ketamine treatment did not alter hippocampal BDNF protein levels in stressed rats. In conclusion, these findings support the idea of a putative role of NMDA receptors in mood-related symptoms, and rapid and robust effects of ketamine in reverting mainly physiological alterations induced by chronic mild stressful situations in rats.