The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats.
Qing Li, Huiran Wu, Shu-Juan Fan, De-Xiang Liu, Hong Jiang, Qian Zhang, F. Pan
Pharmacology, Biochemistry, and Behavior July 23, 2019 DOI: 10.1016/j.pbb.2019.172742 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adolescent rats (28-day old at start) |
| Interventions | Ketamine Ethanol |
| Dose | 20 or 30 mg/kg ketamine; 10% ethanol |
| Duration | 21 days |
| Measures | open field test, forced swimming test, elevated plus maze, Morris water maze, TdT-mediated dUTP Nick-End Labeling (TUNEL), caspase-3, Bax, Bcl-2 |
| Topics | Esketamine Ketamine |
| Key findings | Co-administration of ketamine and ethanol for 21 days increased depressive-like behavior (longer immobility in the forced swimming test) and upregulated TUNEL-positive cells and caspase-3 and Bax expression in the prefrontal cortex, but not the hippocampus, compared with control and single-substance groups. The authors suggest this reflects caspase-dependent apoptosis in the prefrontal cortex. |
Abstract
Ketamine has become increasingly popular in adolescent drug abusers worldwide. Meanwhile, alcohol is usually used by ketamine users. However, little work has been conducted to examine the chronic combined effects of ketamine and ethanol on adolescent brain. Here we probed into the effects of chronic administration of ketamine at recreational doses alone or combined with ethanol on behaviors and neuron damage in an adolescent rat model. 28-day old rats were treated with either 20 or 30 mg/kg ketamine plus or not plus 10% ethanol daily for 21 days. Depressive like behaviors, anxiety like behavior and memory impairment were tested using open field test, forced swimming test, elevated plus maze and Morris water maze. Apoptosis in prefrontal cortex (PFC) and hippocampus (HIP) were determined by the TdT-mediated dUTP Nick-End Labeling (TUNEL) and protein and mRNA levels of caspase-3, Bax and Bcl-2. Results show that co-application of ketamine and ethanol significantly increased immobility time in the forced swimming test, up-regulated TUNEL positive cells and both protein and mRNA expressions of caspase-3 and Bax, compared with the control group and ketamine and ethanol use alone groups in the PFC, but not in the HIP. Our study suggests that chronic co-administration of ketamine and ethanol results in depressive-like behavior and the caspase-dependent apoptosis in the PFC of adolescent rats' brains.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One? Frontiers in Psychiatry May 11, 2021
- Ketamine-Ethanol Combination Decreases Reduced Glutathione Levels and Activates both Intrinsic and Extrinsic Apoptotic Pathways Prior to Neuronal Death in SH-SY5Y Cells. Neurotoxicity Research June 7, 2025
- Decreasing brain activity caused by acute administration of ketamine and alcohol - A randomized, controlled, observer-blinded experimental study. Frontiers in Pharmacology 2024
- One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 4, 2023
Cites 14
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Ketamine use: a review Addiction July 21, 2011
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
and 9 more in the library