Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.
Valentina Castelli, Gianluca Lavanco, Giuseppe Tringali, Cesare D'Amico, Salvatore Feo, Martina di Bartolomeo, Claudio D'Addario, Martin Kuchař, Anna Brancato, Carla Cannizzaro
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie December 1, 2024 DOI: 10.1016/j.biopha.2024.117699 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adolescent Sprague Dawley rat offspring prenatally exposed to THC or vehicle |
| Intervention | THC |
| Dose | 2 mg/kg |
| Duration | Gestational day 5-20 (prenatal exposure), with testing in adolescence |
| Topics | Cannabis |
| Keywords | Excitatory/inhibitory balance Hippocampus Prenatal THC Exposure Sex-related vulnerability Spatial memory |
| Key findings | Prenatal THC exposure caused sex-specific disruption of spatial memory retrieval and flexibility, with males showing greater vulnerability and opposite changes in inhibitory interneuron density compared to females. |
Abstract
The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis. Sprague Dawley dams were exposed to THC (2 mg/kg) or vehicle, from gestational day 5-20. The adolescent progeny of both sexes was tested for: spatial memory retrieval and flexibility in the Barnes Maze; mRNA expression of relevant players of hippocampal synaptic plasticity; density of cholecystokinin-positive basket cells (CCK+BCs) - a major subtype of hippocampal inhibitory interneurons; mRNA expression of the excitatory and inhibitory synaptic proteins neuroligins (Nlgns), as a proxy of synaptic efficiency. Our results show a sex-specific disruption in spatial memory retrieval and flexibility, a male-specific decrease in CCK+BCs density and increase in the expression of markers of neuroplasticity, and consistent changes in the expression of Nlgn-1 and 3 isoforms. Despite a delay in memory retrieval, flexibility of memory was spared in prenatally-THC-exposed female offspring as well as most of the markers of neuroplasticity; a sex-specific increase in CCK+BCs density, and a consistent expression of Nlgn-3 was observed. The current results highlight a major vulnerability to prenatal exposure to THC on memory processing in the male progeny, and sex-specific alterations in the E/I balance and synaptic plasticity.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |
Citations in the library
Cited by 5
- 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 cannabinoid exposure alters excitation-inhibition balance through glutamate and GABA receptor-mediated signaling. Journal of Biological Chemistry July 2026
- Perinatal LC-ω-3-PUFA supplementation offsets prenatal THC-induced cognitive deficit via sex-specific modulation of hippocampal neuroplasticity. European Journal of Pharmacology June 1, 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
- Gestational THC exposure perturbates hippocampal mitochondrial respiration in the memory-impaired adolescent progeny: Is there a role for mitochondrial CB1 receptor? Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 2025
Cites 7
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and 2 more in the library