Effects of combined postweaning social isolation and ketamine administration on schizophrenia-like behaviour in male Sprague Dawley rats.
Khanyiso Bright Shangase, Mluleki Luvuno, Musa V Mabandla
Behavioural Brain Research January 5, 2025 DOI: 10.1016/j.bbr.2024.115214 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | Male Sprague Dawley rats |
| Interventions | Ketamine Social isolation |
| Dose | 16 mg/kg |
| Duration | Four weeks |
| Topics | Ketamine Esketamine |
| Keywords | Aggressive behaviour Double hit Group housed Schizophrenia research Animal behavior studies Neuropharmacology Psychiatric models Social isolation effects |
| Citations | 6 |
| Key findings | The double-hit model (ketamine plus social isolation) induced stronger negative and cognitive symptoms of schizophrenia than either intervention alone. |
Abstract
The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness of treatment on these symptoms. Developing reliable animal model of schizophrenia is vital to advance our understanding on the neurobiological basis of the disorder. Double hit is used to refer to the use of two schizophrenia inducing interventions viz ketamine exposure and social isolation. In this study we aim to investigate the robustness of double hit model of schizophrenia in inducing negative and cognitive symptoms of schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), group housed + ketamine (GHK), isolated + saline (SI), and isolated + ketamine (SIK). A single ketamine dose (16 mg/kg) was administered 3 times a week for four weeks. Isolated animals were housed singly throughout the study. The following behavioural tests were carried out: elevated plus maze, three chamber social interaction, resident intruder tests, and novel object recognition (NOR). The SIK group exhibited high anxiety levels, with increased ACTH, corticosterone and norepinephrine concentration when compared to the other groups. The SIK animals also presented with reduced social interaction and decreased oxytocin concentration. SIK rats were more aggressive towards a juvenile intruder but had low testosterone concentration. The SIK group or double hit model showed impaired visual learning and memory and increased expression of proinflammatory cytokines. This suggest that the double hit model is more robust in inducing negative and cognitive symptoms of schizophrenia than each treatment alone.
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
- Reviewing the ketamine model for schizophrenia Journal of Psychopharmacology November 20, 2013
- Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission IBRO Neuroscience Reports January 3, 2024
- Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia. Molecular Neurobiology August 2020
- Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia. The International Journal of Neuropsychopharmacology November 2016
- Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of 'schizophrenia-like' behaviour in the rat. Psychopharmacology June 2014
and 1 more in the library