Effects of Social Isolation on the Behavior of Wistar Rats Subjected to a Ketamine-Induced Model of Schizophrenia
Isabela Hubbe, Ana Luísa S. Ferreira, Nicole Luiza Rizzotto, Murilo Carvalho, Nicole Bento de Oliveira, Lara Canever, Gabriela Pagani da Silva, João Pedro Veronezi Rohling, Samira Silva Valvassori, Gustavo Antunes Mastella, Mariana B. de Oliveira, Alexandra Ioppi Zugno
Bratislavské lekárske listy/Bratislava medical journal October 22, 2026 DOI: 10.1007/s44411-026-00921-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Sample size | 144 |
| Population | Adult male and female Wistar rats |
| Interventions | Ketamine Social isolation |
| Dose | 25 mg/kg, i.p. |
| Duration | Eight weeks of isolation from postnatal day 60; ketamine administered for seven consecutive days |
| Measures | Open field test (OFT), elevated plus maze (EPM), splash test (ST) |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine increased locomotor activity and reduced rearing, with the rearing reduction more pronounced in females; isolation also reduced rearing. Isolation reduced open-arm exploration only in females and increased grooming latency while reducing grooming events. No significant isolation-by-ketamine interaction was found for any measure, indicating largely independent effects. |
Abstract
Abstract This study aimed to evaluate the impact of chronic social isolation on the behavioral profile of male and female Wistar rats within a ketamine (Ket)-induced model of schizophrenia. A total of 144 adult Wistar rats (male and female) were divided into four experimental groups per sex: (1) Socialized + Saline (Sal) (Control group); (2) Socialized + Ket; (3) Isolated + Sal (Isolated group); (4) Isolated + Ket. Rats in the isolated groups were housed individually from postnatal day 60 (PND 60) for eight weeks. Ket (25 mg/kg, i.p.) was administered for seven consecutive days. Behavioral assessments included the open field test (OFT), elevated plus maze (EPM), and splash test (ST), and data were analyzed by three-way ANOVA (sex × isolation × Ket) followed by Tukey’s post hoc test. In the OFT, Ket increased locomotor activity in both sexes and reduced rearing, with this reduction being more pronounced in females. Isolation also reduced rearing. In the EPM, females spent more time in the open arms than males, and isolation was associated with reduced open-arm exploration only in females. In the ST, isolation increased the latency to initiate grooming and reduced the number of grooming events. No significant interaction between isolation and Ket was observed for any of the parameters analyzed. In conclusion, Ket and social isolation produced distinct and largely independent effects on behavioral domains relevant to schizophrenia, some of which were sex-dependent, and their combination did not yield a synergistic effect. These findings highlight the importance of including both sexes in the characterization of animal models relevant to schizophrenia.
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 6
- Ketamine and olanzapine alter behaviour and prefrontal-cortex BDNF differentially in male and female rats Scientific Reports August 23, 2025
- Combined Low Dose of Ketamine and Social Isolation: A Possible Model of Induced Chronic Schizophrenia-Like Symptoms in Male Albino Rats Brain Science July 1, 2021
- Co-administration of cannabidiol and ketamine induces antidepressant-like effects devoid of hyperlocomotor side-effects. Neuropharmacology June 19, 2021
- Sex Differences in the Pharmacokinetics of Low-dose Ketamine in Plasma and Brain of Male and Female Rats. Journal of Pharmacology and Experimental Therapeutics December 2018
- Ketamine as a prophylactic against stress-induced depressive-like behavior Biological Psychiatry May 4, 2015
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