Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model.
Alexandre Seillier, Alex A Martinez, Andrea Giuffrida
PLoS One 2020 DOI: 10.1371/journal.pone.0230238 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Male rats (Sprague-Dawley or similar, not specified) |
| Interventions | phencyclidine (PCP) d-amphetamine |
| Dose | 0.1, 0.3, 1.0 mg/kg, i.p. |
| Topics | Cannabis |
| Key findings | Only low doses of THC (0.1 mg/kg) reversed PCP-induced social withdrawal and elevated anandamide levels, while higher doses worsened social deficits and disrupted dopamine neuron activity. |
Abstract
Social withdrawal in the sub-chronic phencyclidine (PCP) rat model, a behavioral correlate of the negative symptoms of schizophrenia, results from deficits in brain endocannabinoid transmission. As cannabis intake has been shown to affect negatively the course and expression of psychosis, we tested whether the beneficial effects of endocannabinoid-mediated CB1 activation on social withdrawal in PCP-treated rats (5 mg/kg, twice daily for 7 days)also occurred after administration of Δ9-tetrahydrocannabinol (THC; 0.1, 0.3, 1.0 mg/kg, i.p.). In addition, we assessed whether THC affected two correlates of positive symptoms: 1) motor activity induced by d-amphetamine (0.5 mg/kg, i.p.), and 2) dopamine neuron population activity in the ventral tegmental area (VTA). After the motor activity test, the brains from d-amphetamine-treated animals were collected and processed for measurements of endocannabinoids and activation of Akt/GSK3β, two molecular markers involved in the pathophysiology of schizophrenia. In control rats, THC dose-dependently produced social interaction deficits and aberrant VTA dopamine neuron population activity similar to those observed in PCP-treated animals. In PCP-treated rats, only the lowest dose of THC reversed PCP-induced deficits, as well as PCP-induced elevation of the endocannabinoid anandamide (AEA) in the nucleus accumbens. Last, THC activated the Akt/GSK3β pathway dose-dependently in both control and PCP-treated animals. Taken together, these data suggest that only low doses of THC have beneficial effects on behavioral, neurochemical and electrophysiological correlates of schizophrenia symptoms. This observation may shed some light on the controversial hypothesis of marijuana use as self-medication in schizophrenic patients.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 6
- Molecular Pathways Potentially Involved in Hallucinatory Experiences During Sleep Paralysis: The Emerging Role of β-Arrestin-2 International Journal of Molecular Sciences July 26, 2025
- Acute Ultra Low Dose THC Attenuates Anxiety-Like Behavior in a Mouse Model for Major-Depressive Disorder Journal of Molecular Neuroscience October 12, 2026
- Multidimensional analysis of social withdrawal in the sub-chronic phencyclidine rat model for schizophrenia. Psychopharmacology April 23, 2026
- Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia Current Addiction Reports February 27, 2026
- Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids. Neurobiology of Disease 2023
and 1 more in the library
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