Adolescent Δ-9-tetrahydrocannabinol exposure induces differential acute and long-term neuronal and molecular disturbances in dorsal vs. ventral hippocampal subregions.
Marta De Felice, Chaochao Chen, Mar Rodríguez-ruiz, Hanna J Szkudlarek, Michael Lam, Selvi Sert, Shawn N Whitehead, Ken K-C Yeung, Walter J Rushlow, Steven R Laviolette
Neuropsychopharmacology February 2023 DOI: 10.1038/s41386-022-01496-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical rodent study Peer reviewed |
|---|---|
| Population | Adolescent rodents exposed to THC |
| Intervention | Δ-9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key points | Adolescent THC exposure in rodents produced long-lasting memory deficits and anxiety-like behaviors, together with region-specific molecular and neuronal abnormalities in the dorsal versus ventral hippocampus. The authors report enduring dysregulation of GABA and glutamate levels and dissociable changes in glutamatergic signaling, pyramidal neuron activity, and oscillatory patterns across these regions. |
Abstract
Chronic exposure to Δ-9-tetrahydrocannabinol (THC) during adolescence is associated with long-lasting cognitive impairments and enhanced susceptibility to anxiety and mood disorders. Previous evidence has revealed functional and anatomical dissociations between the posterior vs. anterior portions of the hippocampal formation, which are classified as the dorsal and ventral regions in rodents, respectively. Notably, the dorsal hippocampus is critical for cognitive and contextual processing, whereas the ventral region is critical for affective and emotional processing. While adolescent THC exposure can induce significant morphological disturbances and glutamatergic signaling abnormalities in the hippocampus, it is not currently understood how the dorsal vs. ventral hippocampal regions are affected by THC during neurodevelopment. In the present study, we used an integrative combination of behavioral, molecular, and neural assays in a neurodevelopmental rodent model of adolescent THC exposure. We report that adolescent THC exposure induces long-lasting memory deficits and anxiety like-behaviors concomitant with a wide range of differential molecular and neuronal abnormalities in dorsal vs. ventral hippocampal regions. In addition, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), we show for the first time that adolescent THC exposure induces significant and enduring dysregulation of GABA and glutamate levels in dorsal vs. ventral hippocampus. Finally, adolescent THC exposure induced dissociable dysregulations of hippocampal glutamatergic signaling, characterized by differential glutamatergic receptor expression markers, profound alterations in pyramidal neuronal activity and associated oscillatory patterns in dorsal vs. ventral hippocampal subregions.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 4
- Regulation of neural connectivity and oscillations by cannabinoids: A review. Neuroscience & Biobehavioral Reviews September 7, 2026
- Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats Psychopharmacology April 23, 2026
- Adolescent female rats are resistant to the affective and cognitive impacts of Δ9-tetrahydrocannabinol exposure despite long-lasting molecular and neuronal disturbances in the hippocampal-hypothalamic network. Psychopharmacology November 1, 2025
- Cannabis use and psychotic-like experiences: A systematic review of biological vulnerability, potency effects, and clinical trajectories. Psychiatry Research April 1, 2025
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