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

Abstract

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.

Isolation and structure elucidation of cyclohexanepentol, an anti-psychotic agent from Cissampelos owarensis (P. Beauv.) leaves

“…Administration of ketamine was shown to enhance the release of dopamine and glutamate in the brain striatal region (Hons et al, 2010). Ketamine, an NMDAR antagonist induces hyper locomotion by increasing the number of lines crossed and reducing the ambulation time in mice (Sartim et al, 2021;Zhang et al, 2021). The crude extract of Cissampelos owariensis alongside its fractions were screened for their effect on behavioural studies.…”

Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats

“…We also observed delayed recovery of omission performance following ketamine emergence. In both human ( Ionescu et al, 2018 ) and rodent ( Radford et al, 2018 ; Zhang et al, 2019 , 2021 ) studies, even a single sub-anesthetic dose of ketamine has been shown to produce persistent changes in neural plasticity. Like dexmedetomidine, ketamine is typically administered in low doses as an adjunct with other general anesthetics.…”

Perspective Chapter: Ketamine, Depression, and Gender Bias

“…Different bolus doses were found to induce the protein expression of c-Fos in the amygdala of female rats, not the male rats. Also, in the prefrontal cortex, this expression was modulated by the estrous cycle [61]. The administration of ketamine in female mice exposed to chronic unpredictable mild stress was reported to be mediated via the extracellular-signal-regulated kinase and glucose transporter 3 (ERK/GLUT3) signaling pathway [62].…”