Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.
Valentina Castelli, Gianluca Lavanco, Salvatore Feo, Cesare D'Amico, Vincenzo Micale, Martin Kuchař, Fulvio Plescia, Anna Brancato, Carla Cannizzaro
Pharmaceutics February 17, 2023 DOI: 10.3390/pharmaceutics15020692 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent male Wistar rat offspring prenatally exposed to THC |
| Intervention | THC |
| Dose | 2 mg/kg |
| Duration | Gestational day 5 to 20 |
| Topics | Cannabis Neuroplasticity |
| Keywords | Cb1r expression Adolescent rat offspring Hippocampal excitatory plasticity Prenatal THC Exposure |
| Key findings | Prenatal THC exposure in rats was associated with deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, and altered hippocampal mRNA levels of NMDA receptor subunits, mGluR5, PSD95, Homer1, CB1R, and HINT1. The authors suggest these changes may represent targets for future pharmacological interventions. |
Abstract
Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevated plus maze, and sucrose preference tests, respectively. The gene expression levels of NMDA NR1-2A subunits, mGluR5, and their respective scaffold proteins PSD95 and Homer1, as well as CB1R and the neuromodulatory protein HINT1, were measured in the hippocampus. pTHC offspring exhibited deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, increased NR1-, decreased NR2A- and PSD95-, increased mGluR5- and Homer1-, and augmented CB1R- and HINT1-hippocampal mRNA levels. Our data shows that pTHC is associated with specific impairment in spatial cognitive processing and effectors of hippocampal neuroplasticity and suggests novel targets for future pharmacological challenges.
Comparable studies
Other preclinical and animal studies on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Mice | 2023 | Experimental study | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study | |
| The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Progenitor cells from subventricular and subgranular zones of adult mice brains | 2017 | In vitro experimental study | |
| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 11
- Vaporized Δ9-tetrahydrocannabinol exposure in utero has negative effects on attention in a dose- and sex-dependent manner. Pharmacology, Biochemistry, and Behavior September 1, 2024
- Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits. ACS Chemical Neuroscience February 18, 2026
- Prenatal Δ9-tetrahydrocannabinol exposure rewires glucocorticoid-hippocampal crosstalk and impairs memory under stress in adolescent rat offspring. European Journal of Pharmacology September 15, 2026
- Regulation of neural connectivity and oscillations by cannabinoids: A review. Neuroscience & Biobehavioral Reviews September 7, 2026
- Δ9-Tetrahydrocannabinol Modulates Hippocampal Neurogenesis in Female Wistar Rats: Interaction with Estradiol. Neurochemical Research August 8, 2026
and 6 more in the library
Cites 7
- Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Neuropsychopharmacology January 26, 2020
- 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
- Review of the Endocannabinoid System Biological Psychiatry: Cognitive Neuroscience and Neuroimaging August 1, 2020
- Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone Nature Neuroscience September 11, 2019
- Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure. Molecular Psychiatry January 2017
and 2 more in the library