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Article

Enhanced Fear Memories and Altered Brain Glucose Metabolism (18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague–Dawley Rats

1
Daniel K. Inouye Graduate School of Nursing, Uniformed Services University, Bethesda, MD 20814, USA
2
Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD 20814, USA
3
Biomedical Research Imaging Core (BRIC), Department of Radiology and Radiological Sciences, Uniformed Services University, Bethesda, MD 20814, USA
4
Program in Neuroscience, Uniformed Services University, Bethesda, MD 20814, USA
5
Department of Psychiatry, F. E. Hébert School of Medicine, Uniformed Services University, Bethesda, MD 20814, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Changjong Moon
Int. J. Mol. Sci. 2022, 23(3), 1922; https://doi.org/10.3390/ijms23031922
Received: 21 December 2021 / Revised: 30 January 2022 / Accepted: 4 February 2022 / Published: 8 February 2022
Although women and men are equally likely to receive ketamine following traumatic injury, little is known regarding sex-related differences in the impact of ketamine on traumatic memory. We previously reported that subanesthetic doses of an intravenous (IV) ketamine infusion following fear conditioning impaired fear extinction and altered regional brain glucose metabolism (BGluM) in male rats. Here, we investigated the effects of IV ketamine infusion on fear memory, stress hormone levels, and BGluM in female rats. Adult female Sprague–Dawley rats received a single IV ketamine infusion (0, 2, 10, or 20 mg/kg, over a 2-h period) following auditory fear conditioning (three pairings of tone and footshock). Levels of plasma stress hormones, corticosterone (CORT) and progesterone, were measured after the ketamine infusion. Two days after ketamine infusion, fear memory retrieval, extinction, and renewal were tested over a three-day period. The effects of IV ketamine infusion on BGluM were determined using 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) and computed tomography (CT). The 2 and 10 mg/kg ketamine infusions reduced locomotor activity, while 20 mg/kg infusion produced reduction (first hour) followed by stimulation (second hour) of activity. The 10 and 20 mg/kg ketamine infusions significantly elevated plasma CORT and progesterone levels. All three doses enhanced fear memory retrieval, impaired fear extinction, and enhanced cued fear renewal in female rats. Ketamine infusion produced dose-dependent effects on BGluM in fear- and stress-sensitive brain regions of female rats. The current findings indicate that subanesthetic doses of IV ketamine produce robust effects on the hypothalamic–pituitary–adrenal (HPA) axis and brain energy utilization that may contribute to enhanced fear memory observed in female rats. View Full-Text
Keywords: intravenous ketamine; fear memory; brain imaging; sex differences; stress hormone; post-traumatic stress disorder (PTSD) intravenous ketamine; fear memory; brain imaging; sex differences; stress hormone; post-traumatic stress disorder (PTSD)
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MDPI and ACS Style

Radford, K.D.; Berman, R.Y.; Jaiswal, S.; Kim, S.Y.; Zhang, M.; Spencer, H.F.; Choi, K.H. Enhanced Fear Memories and Altered Brain Glucose Metabolism (18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague–Dawley Rats. Int. J. Mol. Sci. 2022, 23, 1922. https://doi.org/10.3390/ijms23031922

AMA Style

Radford KD, Berman RY, Jaiswal S, Kim SY, Zhang M, Spencer HF, Choi KH. Enhanced Fear Memories and Altered Brain Glucose Metabolism (18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague–Dawley Rats. International Journal of Molecular Sciences. 2022; 23(3):1922. https://doi.org/10.3390/ijms23031922

Chicago/Turabian Style

Radford, Kennett D., Rina Y. Berman, Shalini Jaiswal, Sharon Y. Kim, Michael Zhang, Haley F. Spencer, and Kwang H. Choi. 2022. "Enhanced Fear Memories and Altered Brain Glucose Metabolism (18F-FDG-PET) following Subanesthetic Intravenous Ketamine Infusion in Female Sprague–Dawley Rats" International Journal of Molecular Sciences 23, no. 3: 1922. https://doi.org/10.3390/ijms23031922

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