Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat.
Lindsay Silva, Lauren Harte-Hargrove, Sari Izenwasser, Ashley Frank, Dean Wade, Diana Dow-Edwards
Neuroscience Letters August 18, 2015 DOI: 10.1016/j.neulet.2015.06.033 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male and female adolescent rats |
| Duration | Chronic treatment with assessment at 24 hours and 2 weeks post treatment |
| Measures | [3H] CP55,940 binding |
| Topics | Cannabis |
| Keywords | Adolescence Cb1 receptor expression Delta-9-tetrahydrocannabinol Hippocampus Sex differences |
| Key findings | Chronic adolescent THC exposure downregulated hippocampal CB1 receptors at 24 hours in both sexes. After two weeks of abstinence, downregulation persisted in CA2 in both sexes, and additionally in CA1 and CA3 in females, while dentate gyrus expression normalized. The authors suggest these persistent reductions are more widespread in female adolescents. |
Abstract
Marijuana use by adolescents has been on the rise since the early 1990s. With recent legalization and decriminalization acts passed, cannabinoid exposure in adolescents will undoubtedly increase. Human studies are limited in their ability to examine underlying changes in brain biochemistry making rodent models valuable. Studies in adult and adolescent animals show region and sex specific downregulation of the cannabinoid 1 (CB1) receptor following chronic cannabinoid treatment. However, although sex-dependent changes in behavior have been observed during the drug abstinence period following adolescent cannabinoid exposure, little is known about CB1 receptor expression during this critical time. In order to characterize CB1 receptor expression following chronic adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we used [(3)H] CP55,940 binding to assess CB1 receptor expression in the dentate gyrus and areas CA1, CA2, and CA3 of the hippocampus in both male and female adolescent rats at both 24h and 2 weeks post chronic THC treatment. Consistent with other reported findings, we found downregulation of the CB1 receptor in the hippocampal formation at 24h post treatment. While this downregulation persisted in both sexes following two weeks of abstinence in the CA2 region, in females, this downregulation also persisted in areas CA1 and CA3. Expression in the dentate gyrus returned to the normal range by two weeks. These data suggest that selective regions of the hippocampus show persistent reductions in CB1 receptor expression and that these reductions are more widespread in female compared to male adolescents.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 8
- Adolescent cannabinoid vapour exposure sex-dependently alters the relationship between vulnerability traits and ethanol self-administration and modifies naltrexone actions on ethanol intake in rats. Neuropharmacology May 1, 2026
- Envisioning Cannabinoid CB1 Receptor Biased Signaling as a Therapeutic Target for Schizophrenia. American Journal of Psychiatry April 17, 2026
- Altered Network Function in Hippocampus After Sub-Chronic Activation of Cannabinoid Receptors in Early Adolescence. International Journal of Molecular Sciences December 18, 2025
- Altered network function in hippocampus after sub-chronic activation of Cannabis receptors in peri-adolescence. bioRxiv : the preprint server for biology September 21, 2025
- Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [3H] SR141716A receptor binding in the rat brain. Life Sciences August 15, 2023
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Cites 7
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- Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat. Neurotoxicology and Teratology 2010
- Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus August 2009
- The depressive phenotype induced in adult female rats by adolescent exposure to THC is associated with cognitive impairment and altered neuroplasticity in the prefrontal cortex. Neurotoxicity Research May 2009
and 2 more in the library