Effects of subanesthetic intravenous ketamine infusion on neuroplasticity-related proteins in male and female Sprague-Dawley rats

IBRO Neuroscience Reports

Kwang H. Choi¹  Haley F. Spencer¹  Michael Zhang²  Kennett D. Radford²  Rina Y. Berman³ 

[1] Center for the Study of Traumatic Stress, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;Department of Psychiatry, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;Program in Neuroscience, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA;

关键词: Intravenous ketamine;    Estrous cycle, Brain-derived neurotrophic factor;    C-Fos;    Extracellular signal-regulated kinase;    Sex differences;   

DOI  :  

来源: DOAJ

【 摘 要 】

Although ketamine, a multimodal dissociative anesthetic, is frequently used for analgesia and treatment-resistant major depression, molecular mechanisms of ketamine remain unclear. Specifically, differences in the effects of ketamine on neuroplasticity-related proteins in the brains of males and females need further investigation. In the current study, adult male and female Sprague-Dawley rats with an indwelling jugular venous catheter received an intravenous ketamine infusion (0, 10, or 40 mg/kg, 2-h), starting with a 2 mg/kg bolus for ketamine groups. Spontaneous locomotor activity was monitored by infrared photobeams during the infusion. Two hours after the infusion, brain tissue was dissected to obtain the medial prefrontal cortex (mPFC), hippocampus including the CA1, CA3, and dentate gyrus, and amygdala followed by Western blot analyses of a transcription factor (c-Fos), brain-derived neurotrophic factor (BDNF), and phosphorylated extracellular signal-regulated kinase (pERK). The 10 mg/kg ketamine infusion suppressed locomotor activity in male and female rats while the 40 mg/kg infusion stimulated activity only in female rats. In the mPFC, 10 mg/kg ketamine reduced pERK levels in male rats while 40 mg/kg ketamine increased c-Fos levels in male and female rats. Female rats in proestrus/estrus phases showed greater ketamine-induced c-Fos elevation as compared to those in diestrus phase. In the amygdala, 10 and 40 mg/kg ketamine increased c-Fos levels in female, but not male, rats. In the hippocampus, 10 mg/kg ketamine reduced BDNF levels in male, but not female, rats. Taken together, the current data suggest that subanesthetic doses of intravenous ketamine infusions produce differences in neuroplasticity-related proteins in the brains of male and female rats.

【 授权许可】

Unknown