One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats.
C. C. M. D. Menezes da Silveira, Sabrina de Carvalho Cartágenes, Natália Harumi Correa Kobayashi, S. V. Farias, Fábio José Coelho de Souza-Junior, L. M. P. Fernandes, A. F. Do Prado, W. A. Aragão, R. R. Lima, W. A. Ferreira, E. D. de Oliveira, Fernando Augusto Rodrigues Mello, R. Burbano, E. Fontes-Júnior, C. S. F. Maia
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie April 4, 2023 DOI: 10.1016/j.biopha.2023.114641 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent female rats |
| Interventions | Ethanol Ketamine |
| Duration | 3 consecutive days (binge-like pattern), with assessments during early withdrawal |
| Measures | Open field, Elevated plus maze, Forced swim test, Reactive oxygen species (ROS), Antioxidant capacity against peroxyl radicals (ACAP), Lipid peroxidation |
| Topics | Esketamine Ketamine |
| Key findings | Ethanol and ketamine, alone or combined, produced anxiety- and depressive-like behaviors in adolescent female rats during early withdrawal, without synergistic behavioral effects. However, the combination aggravated oxidative damage in the prefrontal cortex and hippocampus compared with either drug alone, indicating that co-abuse may intensify brain oxidative injury without a matching behavioral worsening. |
Abstract
Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype. DATA AVAILABILITY STATEMENT: The datasets used and/or analyzed during the current investigation are available upon reasonable request from the corresponding author.
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
Cites 4
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine and depression: a narrative review Drug Design, Development and Therapy August 1, 2019
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
- The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats. Pharmacology, Biochemistry, and Behavior July 23, 2019