Ketamine Administration Leads to Learning-Memory Dysfunction and Decreases Serum Brain-Derived Neurotrophic Factor in Rats

Abstract

Objective: This study investigated the effects of acute or chronic ketamine administration on learning and memory function as well as levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and blood in order to explore the potential correlation between learning-memory dysfunction and ketamine. Methods: Rats were treated with 25 mg/kg ketamine for 3 d (n = 20) or 14 d (n = 20). Saline-treated rats were used as controls. The Morris water maze test was used to evaluate spatial learning and memory after 10 d of withdrawal. The level of BDNF in serum and the hippocampus were measured by ELISA. Results: The number of platform crossings and residence time in the target platform quadrant were significantly reduced in ketamine 3 d and 14 d groups than in the saline controls (both p < 0.05). In addition, the average escape latency of ketamine 3 d and 14 d groups were significantly longer than that of the saline 3 d and 14 d groups (p < 0.0001), respectively. Further examination found that only serum samples from ketamine 14 d group showed significantly decreased BDNF level compared to that from saline 14 d groups (p < 0.05). However, no differences were detected in hippocampus samples. Conclusion: Chronic ketamine exposure (25 mg/kg) causes spatial learning and memory deficits in SD rats, which may be associated with decreased serum BDNF levels.

Cellular messenger molecules mediating addictive drug-induced cognitive impairment: cannabinoids, ketamine, methamphetamine, and cocaine

“…In addition, ketamine can affect neurodevelopment. The serum BDNF concentration was significantly lower in ketamine-treated rats than in the normal group, with the former group animals exhibiting memory deficits in the Morris water maze [30]. In human research, longterm ketamine users showed poor activation in the hippocampal complex, as well as impaired spatial memory [31].…”

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

“…Most previous studies found positive changes in BDNF when measured within 30–60 min after bolus ketamine injection, while our samples were analyzed 2 h post-ketamine infusion. Accordingly, previous reports describe no changes in hippocampal BDNF when measured between 4 h up to 10 days post-ketamine injection, further suggesting a transient regulation of BDNF levels after ketamine administration ( Li et al, 2020 , Medeiros et al, 2021 , Saur et al, 2017 ). Thus, a subsequent study is warranted to investigate effects of IV ketamine infusion on BDNF levels in different brain regions of animals at multiple time points.…”

Ketamine alleviates fear memory and spatial cognition deficits in PTSD rat model via BDNF signaling pathway of hippocampus and amygdala

“…Information acquisition and renewal are important processes of learning and memory,and ketamine induced signi cant changes in the expression of glutamate receptors in brain areas relevant for renewal and contextual memory [43]. These ndings may explain the result that ketamine can signi cantly reduce the freezing time, as well as improve the spatial memory and learning ability of rats exposed to SPS&S.…”