Investigating the "two-hit hypothesis": Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice.
Elisa Guma, Lani Cupo, Weiya Ma, Daniel Gallino, Luc Moquin, Alain Gratton, Gabriel A Devenyi, M Mallar Chakravarty
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2023 DOI: 10.1016/j.pnpbp.2022.110642 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Longitudinal Peer reviewed |
|---|---|
| Population | Mice prenatally exposed to poly I:C or vehicle and postnatally exposed to THC or vehicle |
| Interventions | Poly I:C THC |
| Dose | poly I:C 5 mg/kg; THC 5 mg/kg intraperitoneal |
| Duration | Prenatal exposure at gestational day 9; adolescent THC from postnatal day 28 to 45; MRI at PND 25, 50, and 85 |
| Measures | magnetic resonance imaging (MRI), behavioural tests for anxiety-like, social, and sensorimotor gating, post-mortem assessment of CB1 and CB2 receptor expressing cells |
| Topics | Cannabis |
| Keywords | Adolescent cannabis use Brain development Environmental risk factors Maternal immune activation Neuropsychiatric disorders |
| Key findings | Combined prenatal MIA and adolescent THC exposure produced only subtle neurodevelopmental deviations and subthreshold anxiety-like behaviors in mice, with sex-dependent patterns of brain-behavior covariation. Density of CB1 and CB2 receptor-positive cells was significantly decreased in all mice exposed to MIA, THC, or both, suggesting the endocannabinoid system is sensitive to these exposures. |
Abstract
Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood. Mice were prenatally exposed to viral mimetic, poly I:C (5 mg/kg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mg/kg, intraperitoneal) or vehicle during adolescence (postnatal day [PND]28-45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus). Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both. These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
- Disruption of Reelin signaling in a dual-hit mouse model of schizophrenia: impact of postnatal Δ9-tetrahydrocannabinol exposure in a maternal immune activation model Translational Psychiatry July 16, 2026
- Divergent outcomes of delta 9 - tetrahydrocannabinol (THC) in adolescence on mesocortical dopamine and cognitive development in male and female mice. Psychopharmacology October 2025
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