Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats.
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.
Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Lêda S B
LS
Garcia
Clarissa M
CM
Comim
Samira S
SS
Valvassori
Gislaine Z
GZ
Réus
Laura
L
Stertz
Flávio
F
Kapczinski
Elaine C
EC
Gavioli
João
J
Quevedo
D000311:Adrenal Glands / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects; D005508:Food Deprivation; D005518:Food Preferences / Q000187:drug effects; D007649:Ketamine / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D012934:Social Isolation; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D013997:Time Factors; D014868:Water Deprivation
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone