Adolescent Exposure to a THC-Rich Cannabis Extract Produces Genotype-Dependent Effects on Cognition and Glial Morphology in Serine Racemase Mutant Mice.
Igor F Rangel, Melissa Chaves, Iohanna Pagnoncelli, Isabelle Medeiros, Felipe Pinheiro, Lorena Fortuna, Luiza Castello-Branco, Ernesto Diaz Roch, Virgínia Martins Carvalho, Flavia Regina Souza Lima, Rogério Panizzutti, Luciana Romão
Journal of Neurochemistry September 2026 DOI: 10.1111/jnc.70559 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experimental study Peer reviewed |
|---|---|
| Population | SrrY269* serine racemase mutant mice and wild-type mice exposed to a THC-rich cannabis extract during adolescence |
| Intervention | THC-rich cannabis extract |
| Dose | escalating oral doses |
| Duration | Exposure during adolescence with evaluation in adulthood |
| Measures | prepulse inhibition, spatial object recognition memory, open field test, amino acid quantification, glial morphometric analyses |
| Topics | Cannabis |
| Keywords | D‐serine Astrocytes Cannabinoids Microglia Neuroinflammation Schizophrenia Serine racemase |
| Key findings | Adolescent exposure to a THC-rich cannabis extract prevented prepulse inhibition and spatial object recognition deficits and attenuated microglial and astrocytic alterations in adult SrrY269* mice, while transiently impairing sensorimotor gating and inducing a distinct astrocytic phenotype in wild-type mice. The authors argue that genetic background may be an important determinant of the long-term neurodevelopmental consequences of adolescent THC-rich cannabis exposure. |
Abstract
Adolescent cannabis exposure has been associated with an increased risk of schizophrenia; however, how genetic vulnerability shapes the long-term consequences of adolescent cannabinoid exposure remains poorly understood. Δ9-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis and the predominant cannabinoid in the THC-rich cannabis extract used here, primarily activates cannabinoid type 1 receptors (CB1). In parallel, reduced availability of D-serine, an endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs), has been implicated in the pathophysiology of schizophrenia. Here, we investigated whether adolescent exposure to a THC-rich cannabis extract modulated long-term behavioral, neurochemical, and glial outcomes in serine racemase mutant (SrrY269*) mice, a genetic model characterized by reduced D-serine levels and schizophrenia-relevant phenotypes. Mice received escalating oral doses of the THC-rich cannabis extract during adolescence and were evaluated in adulthood using behavioral assays, amino acid quantification, and glial morphometric analyses. Adolescent exposure to the THC-rich cannabis extract prevented deficits in prepulse inhibition and spatial object recognition memory in adult SrrY269* mice, while transiently impairing sensorimotor gating in wild-type animals. Irrespective of genotype, mice exposed to the THC-rich cannabis extract spent more time in the center of the open field in adulthood. In behaviorally tested SrrY269* mice, reduced hippocampal microglial branching was attenuated following adolescent treatment. In an independent behavior-naïve cohort, SrrY269* mice exhibited marked astrocytic morphological alterations, several of which were also attenuated by adolescent exposure to the THC-rich cannabis extract. In contrast, the same treatment induced a distinct astrocytic phenotype in wild-type mice. Adolescent exposure to the THC-rich cannabis extract did not alter hippocampal or prefrontal cortical levels of D-serine or other amino acids involved in NMDAR signaling in adulthood. These findings indicate that adolescent exposure to a THC-rich cannabis extract produces genotype-dependent long-term effects, preventing specific behavioral deficits and attenuating independently assessed microglial and astrocytic alterations in SrrY269* mice, while producing adverse behavioral and astrocytic outcomes in wild-type animals. Genetic background may therefore be an important determinant of the long-term neurodevelopmental consequences of adolescent exposure to THC-rich cannabis extracts.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 4
- The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology International Journal of Molecular Sciences February 15, 2023
- Differences in Inhibitory Control and Resting Brain Metabolism between Older Chronic Users of Tetrahydrocannabinol (THC) or Cannabidiol (CBD)—A Pilot Study Brain Sciences June 23, 2022
- Dos(e)Age: Role of Dose and Age in the Long-Term Effect of Cannabinoids on Cognition Molecules February 1, 2022
- Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons. Molecular Psychiatry April 2019