Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.
Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist and several studies have pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of depression. The present study was aimed to evaluate the behavioral and physiological effects of administration of memantine in rats exposed to the chronic mild stress (CMS) model. To this aim, after 40 days of exposure to CMS procedure, rats were treated with memantine (20 mg/kg) for 7 days. In this study, sweet food consumption, adrenal gland weight, corticosterone levels, and brain-derived-neurotrophic factor (BDNF) protein levels in the prefrontal cortex, hippocampus and amygdala were assessed. Our results demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, and an increase of corticosterone levels in rats, but did not alter BDNF protein levels in the rat brain. Memantine treatment reversed anhedonia and the increase of adrenal gland weight, normalized corticosterone levels and increased BDNF protein levels in the prefrontal cortex in stressed rats. Finally, these findings further support the hypothesis that NMDA receptor antagonists such as memantine could be helpful in the pharmacological treatment of depression.
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. gislainezilli@hotmail.com
Gislaine Z
GZ
Réus
Helena M
HM
Abelaira
Roberto B
RB
Stringari
Gabriel R
GR
Fries
Flávio
F
Kapczinski
João
J
Quevedo
D000311:Adrenal Glands / Q000187:drug effects; D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D003345:Corticosterone