CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration
Nafsika Poulia, Foteini Delis, Charalampos Brakatselos, George Ntoulas, M. Asprogerakas, Katerina Antoniou
Frontiers in Pharmacology October 27, 2021 DOI: 10.3389/fphar.2021.746935 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ketamine Cannabidiol |
| Dose | 30 mg/kg (i.p.) ketamine |
| Duration | 10-day chronic ketamine administration, with subsequent chronic cannabidiol treatment |
| Topics | CBD Esketamine Ketamine |
| Key findings | Chronic ketamine (30 mg/kg i.p., 10 days) increased motor activity and produced region-dependent changes in NMDA and AMPA receptor expression and ERK1/2 phosphorylation in rats; subsequent chronic cannabidiol treatment reversed the hyperactivity to normal and modified the glutamatergic and ERK1/2 alterations in a region-dependent manner. The authors propose these findings support cannabidiol's antipsychotic potential in a chronic ketamine model of schizophrenia-like symptomatology. |
Abstract
Clinical evidence and experimental studies have shown the psychotomimetic properties induced by ketamine. Moreover, acute or chronic ketamine (KET) administration has been widely used for modeling schizophrenia-like symptomatology and pathophysiology. Several studies have reported the antipsychotic potential of cannabidiol (CBD), while there is limited information on the cannabidiol effect on KET-induced schizophrenia-like impairments. Therefore, the goal of the present study was to evaluate neuroplastic changes induced by repeated KET administration, which is used as an experimental model of schizophrenia—with a behavioral focus on positive-like symptomatology– and to assess the modulatory role of CBD treatment. The present findings have shown a robust increase in motor activity in KET-treated rats, following a 10-day period of chronic administration at the sub-anesthetic dose of 30 mg/kg (i.p), that was reversed to normal by subsequent chronic CBD treatment. Concerning the expression of glutamate receptors, the current findings have shown region-dependent KET-induced constitutional alterations in NMDA and AMPA receptors that were modified by subsequent CBD treatment. Additionally, repeated KET administration increased ERK1/2 phosphorylation state in all regions examined, apart from the ventral hippocampus that was modulated by subsequent CBD treatment. The present results show, for the first time, a stimulated motor output coupled with a specific glutamatergic-related status and ERK1/2 activation following chronic KET administration that were attenuated by CBD treatment, in a region-dependent manner. These findings provide novel information concerning the antipsychotic potential of CBD using a specific design of chronic KET administration, thus contributing to experimental approaches that mirror the symptomatology and pathophysiology of schizophrenia.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 3
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model. Schizophrenia Research April 1, 2025
- Unraveling Cannabidiol's Dual Modulatory Role in Schizophrenia: Network Pharmacology and In Vivo Validation of Neuroinflammatory and Behavioral Modulation Molecular Neurobiology December 10, 2025
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