Acute ketamine withdrawal disrupts memory and monoaminergic neurotransmission in adolescent female rats.
Lucas Villar Pedrosa Da Silva Pantoja, Luiza Fernanda Ramos Soares, Brenda Costa Da Conceição, Taiana Cristina Carvalheiro-Simas, Diandra Araújo Da Luz, Rui Daniel Prediger, Geanne Matos De Andrade, Enéas Andrade Fontes-Junior, Bruno Gonçalves Pinheiro, Sabrina de Carvalho Cartágenes, Cristiane Socorro Ferraz Maia
Behavioural Brain Research March 28, 2026 DOI: 10.1016/j.bbr.2026.116048 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Adolescent female Wistar rats |
| Intervention | intranasal ketamine |
| Dose | 10 mg/kg/day |
| Duration | Three consecutive days of administration, with behavioral testing starting 24 hours after the last dose |
| Topics | Ketamine Esketamine |
| Keywords | Adolescence Cognition Memory Monoamines Withdrawal |
| Key findings | Early ketamine withdrawal after acute exposure impaired episodic, social, and working memory and reduced serotonin and norepinephrine levels in the hippocampus and prefrontal cortex of adolescent female rats. |
Abstract
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs misuse which may contribute to the development of psychiatric disorders. Ketamine, an NMDA receptor antagonist, is an anesthetic agent used in a recreational manner in night clubs and raves, especially by intranasal route. The psychedelic effects of ketamine include euphoria, reward and mood swings, leading to an altered state of consciousness. Ketamine use has increased among adolescents and young adults, becoming a relevant global public health concern. At these events, drug consumption is often episodic but intense, which may disrupt diverse neuromodulation processes leading to behavioral impairments. Here, we investigated the mnemonic consequences of ketamine withdrawal following recreational exposure in adolescent female rats. To mimic weekend recreational use, adolescent female Wistar rats (n = 8 animals per group) received intranasal ketamine or saline (10 mg/kg/day) for three consecutive days. Twenty-four hours after the last ketamine administration, animals were submitted to a battery of behavioral tasks including novel object recognition, social recognition and Y-maze paradigms to assess episodic, social and working memories. Hippocampal and prefrontal cortex samples were collected for neurochemical analysis. Early ketamine withdrawal following acute exposure impaired all memory types evaluated in the current study. Additionally, a significant reduction in serotonin and norepinephrine levels were observed in the hippocampus and prefrontal cortex of ketamine exposure rats. These findings indicated cognitive and monoaminergic impairments in adolescent female rats at early ketamine withdrawal periods following acute exposure.
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 26
- 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
- A Review of the Nonmedical Use of Ketamine: Use, Users and Consequences Journal of Psychoactive Drugs December 1, 2000
- A REVIEW OF KETAMINE ABUSE AND DIVERSION Depression and Anxiety August 1, 2016
- Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics July 1, 2019
and 21 more in the library