Sexually Dimorphic Effects of a Single Neonatal Δ9-tetrahydrocannabinol Exposure on Neuronal Dendritic Morphology and Cognitive Functions in Rats.
Meetu Wadhwa, Gregory A Chinn, Katrina Duong, Jennifer Sasaki Russell, Judith Hellman, Jeffrey W Sall
Cannabis and Cannabinoid Research February 1, 2026 DOI: 10.1177/25785125251387835 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female Sprague Dawley rat pups |
| Intervention | THC |
| Dose | 5 mg/kg |
| Duration | Single injection at postnatal day 3; behavioral testing at postnatal weeks 6-8 |
| Topics | Cannabis Neuroplasticity |
| Keywords | Cannabinoids Cortex Dendrite Hippocampus Pyramidal neurons Sexual dimorphism Spatial memory |
| Key findings | Neonatal THC exposure induced spatial memory deficits in female but not male rats and reduced dendritic complexity and spine density in cortical and hippocampal neurons of both sexes. |
Abstract
Cannabis consumption among adults, including pregnant and breastfeeding women, continues to rise. However, the long-term effects of early-life exposure to cannabinoids on brain development remain unclear. Δ9-tetrahydrocannabinol (THC) is the main psychoactive cannabinoid in cannabis and is an agonist of cannabinoid type 1 receptor, a critical component of the endocannabinoid system (ECS) that functions in normal pre- and postnatal brain development. We hypothesized that perinatal exposure to THC perturbs ECS-regulated neurodevelopment and leads to lasting cognitive effects in later life. Male and female Sprague Dawley rat pups received a single intraperitoneal injection of THC (5 mg/kg) or vehicle (sesame oil) at postnatal day 3. At postnatal weeks 6-8, animals were assessed for spatial memory and anxiety-like behavior using the Barnes maze, open field, and elevated plus maze. Following behavioral testing, brains were processed using Golgi-Cox staining to examine dendritic morphology and spine density in the frontal cortex and hippocampus. THC exposure during the neonatal period induced a spatial memory deficit later in young adult female, but not male, rats. Anxiety-like behavior was not altered in either sex. THC-exposed animals of both sexes exhibited decreased spine density reductions, as well as decreases in dendritic length, branching, and complexity in cortical and hippocampal (cornu ammonis 1 [CA1], CA3, dentate gyrus) neurons. These findings demonstrate that a single neonatal THC exposure induces long-lasting, sex-dependent cognitive impairment and structural alterations in cortical and hippocampal neurons in rats. Our results underscore the vulnerability of the developing brain to cannabinoid exposure.