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 via PubMed
Summary
AI-generated from the abstractAdolescent female rats that received intranasal ketamine for three consecutive days, mimicking weekend recreational use, showed impairments in episodic, social, and working memory 24 hours after the last dose. The memory deficits were accompanied by reduced serotonin and norepinephrine levels in the hippocampus and prefrontal cortex. The findings indicate that early ketamine withdrawal following acute exposure disrupts cognition and monoamine signaling in the adolescent female brain.
Study at a glance
| 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 |
| Keywords | Adolescence Cognition Memory Monoamines |
| Key finding | 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.