Effects of Ketamine on Rodent Fear Memory.

Kwang H Choi,Haley F Spencer,Michael Zhang,Kennett D Radford,Rina Y Berman

doi:10.3390/ijms21197173

Kwang H Choi, Haley F Spencer + Show 3 more

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https://doi.org/10.3390/ijms21197173

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Abstract

Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic stress disorder (PTSD) remains controversial. To address these concerns, preclinical studies have investigated the effects of ketamine administration on fear memory and stress-related behaviors in laboratory animals. Despite a well-documented line of research examining the effects of ketamine on fear memory, there is a lack of literature reviews on this important topic. Therefore, this review article summarizes the current preclinical literature on ketamine and fear memory with a particular emphasis on the route, dose, and timing of ketamine administration in rodent fear conditioning studies. Additionally, this review describes the molecular mechanisms by which ketamine may impact fear memory and stress-related behaviors. Overall, findings from previous studies are inconsistent in that fear memory may be increased, decreased, or unaltered following ketamine administration in rodents. These conflicting results can be explained by factors such as the route, dose, and timing of ketamine administration; the interaction between ketamine and stress; and individual variability in the rodent response to ketamine. This review also recommends that future preclinical studies utilize a clinically relevant route of administration and account for biological sex differences to improve translation between preclinical and clinical investigations.

Highlights

Ketamine has become a multi-purpose tool within the field of medicine for a variety of indications from trauma analgesia to a treatment for depression and post-traumatic stress disorder (PTSD)
Attenuated increase in CORT after predator-scent stress exposure Effect nullified by GluN2B antagonist ifenprodil
Increased p-extracellular signal-regulated kinase (ERK) and p-AKT Effect nullified by mammalian target of rapamycin (mTOR) antagonist rapamycin

Summary

Introduction

Ketamine has become a multi-purpose tool within the field of medicine for a variety of indications from trauma analgesia to a treatment for depression and post-traumatic stress disorder (PTSD). Due to the inherent moral dilemmas of conducting prospective clinical experiments involving traumatic events and stress-related disorders in humans, researchers often turn to preclinical rodent models to explore ketamine’s effects on fear memory and PTSD-like behaviors. This review aims to describe the most recent preclinical literature that has explored the effects of peri-trauma ketamine administration on rodent fear memory and PTSD-like behaviors with consideration of the route, dose, and timing of ketamine administration along with additional variables that may affect ketamine effects on fear memory. This review summarizes the potential biological mechanisms by which ketamine may interfere with fear memory in rodents and suggests recommendations for future preclinical studies that will enhance clinical translation

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