The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology
Martina di Bartolomeo, Tibor Stark, Serena di Martino, Fabio Arturo Iannotti, Jana Kučerová, Giovanni Luca Romano, Martin Kuchař, Samuele Laudani, Petr Palivec, Fabiana Piscitelli, Carsten T. Wotjak, Claudio Bucolo, Filippo Drago, Vincenzo Di Marzo, Claudio D’addario, Vincenzo Micale
International Journal of Molecular Sciences February 15, 2023 DOI: 10.3390/ijms24043907 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adult rats |
| Interventions | prenatal methylazoxymethanol acetate (MAM) perinatal THC peripubertal Δ9-tetrahydrocannabinol (aTHC) |
| Topics | Cannabis |
| Keywords | Dopaminergic Schizophrenia object-oriented programming Prefrontal cortex Cannabinoid Psychosis Cognitive deficit Endocrinology Cognition Receptor Cognitive impairment |
| Citations | 23 |
| Key findings | Peripubertal THC exposure reversed cognitive deficits in rats prenatally exposed to MAM by modulating dopamine receptor gene expression, but did not exacerbate the altered phenotype in rats perinatally exposed to THC. |
Abstract
Adolescent exposure to cannabinoids as a postnatal environmental insult may increase the risk of psychosis in subjects exposed to perinatal insult, as suggested by the two-hit hypothesis of schizophrenia. Here, we hypothesized that peripubertal Δ9-tetrahydrocannabinol (aTHC) may affect the impact of prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC) exposure in adult rats. We found that MAM and pTHC-exposed rats, when compared to the control group (CNT), were characterized by adult phenotype relevant to schizophrenia, including social withdrawal and cognitive impairment, as revealed by social interaction test and novel object recognition test, respectively. At the molecular level, we observed an increase in cannabinoid CB1 receptor (Cnr1) and/or dopamine D2/D3 receptor (Drd2, Drd3) gene expression in the prefrontal cortex of adult MAM or pTHC-exposed rats, which we attributed to changes in DNA methylation at key regulatory gene regions. Interestingly, aTHC treatment significantly impaired social behavior, but not cognitive performance in CNT groups. In pTHC rats, aTHC did not exacerbate the altered phenotype nor dopaminergic signaling, while it reversed cognitive deficit in MAM rats by modulating Drd2 and Drd3 gene expression. In conclusion, our results suggest that the effects of peripubertal THC exposure may depend on individual differences related to dopaminergic neurotransmission.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 4
- 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
- Adolescent Exposure to a THC-Rich Cannabis Extract Produces Genotype-Dependent Effects on Cognition and Glial Morphology in Serine Racemase Mutant Mice. Journal of Neurochemistry September 2026
- Prenatal THC exposure and binge-like alcohol drinking in early adolescence: From sex-specific drinking vulnerability to abnormal endocannabinoid-dopamine nexus in the nucleus accumbens. Journal of Psychopharmacology February 27, 2026
- The marijuana-schizophrenia multifaceted nexus: Connections and conundrums towards neurophysiology. Computational biology and chemistry December 2023
Cites 6
- Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research Frontiers in Pharmacology June 21, 2017
- Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia Neurotoxicity Research July 1, 2017
- Behavioral and Pharmacokinetic Profile of Indole-Derived Synthetic Cannabinoids JWH-073 and JWH-210 as Compared to the Phytocannabinoid Δ9-THC in Rats Frontiers in Neuroscience October 23, 2018
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
- Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Δ9-tetrahydrocannabinol-exposed rats. Pharmacological Research February 2021
and 1 more in the library