Detrimental effects of adolescent escalating low-dose Δ9 -tetrahydrocannabinol leads to a specific bio-behavioural profile in adult male rats.
Nafsika Poulia, Foteini Delis, Charalampos Brakatselos, Alexia Polissidis, Yassemi Koutmani, Nikolaos Kokras, Christina Dalla, Panagiotis K Politis, Katerina Antoniou
British Journal of Pharmacology April 2021 DOI: 10.1111/bph.15394 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adolescent male Sprague-Dawley rats followed into adulthood |
| Intervention | THC |
| Dose | escalating low-dose of THC |
| Measures | object location task, Morris water maze test |
| Topics | Neuroplasticity Cannabis |
| Keywords | Adolescent Biochemical pharmacology Cannabinoid Cognition Neuronal plasticity Translational pharmacology |
| Key findings | Adolescent low-dose THC exposure in rats increased adult spontaneous locomotion and impaired spatial memory on the object location task and Morris water maze, without affecting prepulse inhibition or attentional set-shifting. These behavioural changes were accompanied by region-specific dopaminergic alterations, prefrontal CB1 receptor up-regulation, reduced hippocampal SOX2- and doublecortin-positive cells, and lower BDNF in hippocampus and prefrontal cortex. The authors argue this model shows cognitive and neurogenic harm without the overt psychotic-like effects reported in high-dose THC studies. |
Abstract
Adolescent cannabis use is associated with adult psychopathology. When Δ9 -tetrahydrocannabinol (THC), mainly in high doses, is administered to adolescence rats there are also long lasting effects in adults. This study aims to determine the specific adult bio-behavioural profile after adolescent low-dose THC, which better mirrors adolescent recreational cannabis use. Adolescent male Sprague-Dawley rats were treated with escalating low-dose of THC. In adulthood, they were evaluated for their spontaneous locomotion, sensorimotor gating, higher order and spatial cognitive functions. Dopaminergic activity and cannabinoid receptor expression were measured in distinct brain regions. Hippocampal neurogenic activity of neural stem cells was determined and protein levels of neuroplasticity-related biomarkers were quantified. Adolescent low-dose THC exposure increased spontaneous open-field activity, without affecting prepulse inhibition and attentional set-shifting performance. Region-specific dopaminergic alterations and CB1 receptor up-regulation in the prefrontal cortex were observed. Impaired spatial memory, as assessed with the object location task and Morris water maze test, was associated with significantly decreased proliferative activity (SOX2-positive cells), neurogenic potential (decreased doublecortin-positive cells) in the adult hippocampus and defective neuroplasticity, including reduced BDNF expression in the hippocampus and prefrontal cortex. Our findings reveal the adverse impact of adolescent low-dose THC on the psychomotor profile, dopaminergic neurotransmission, compensatory cannabinoid receptor response, cognition-related neurobiological and behavioural functions. Our adolescent low-dose THC animal model does not induce tangible psychotic-like effects, such as those reported in high-dose THC studies, but it impairs cognitive functions and points to hippocampal vulnerability and disrupted neurogenesis.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 18
- Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review. Mol Med December 19, 2024
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats. Psychopharmacology February 1, 2025
- 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
- Effects of psychedelics on neurogenesis and brain plasticity: A systematic review bioRxiv (Cold Spring Harbor Laboratory) July 20, 2023
and 13 more in the library
Cites 14
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and 9 more in the library