Sex, drugs, and adult neurogenesis: sex-dependent effects of escalating adolescent cannabinoid exposure on adult hippocampal neurogenesis, stress reactivity, and amphetamine sensitization.
Tiffany T-Y Lee, Steven R Wainwright, Matthew N Hill, Liisa A M Galea, Boris B Gorzalka
Hippocampus March 2014 DOI: 10.1002/hipo.22221 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adult male and female Sprague-Dawley rats exposed to HU-210 or vehicle during adolescence |
| Intervention | HU-210 |
| Dose | 25, 50, and 100 µg/kg escalating doses |
| Duration | HU-210 administered from postnatal day 35 to 46; assessments in adulthood up to postnatal day 134 |
| Measures | BrdU-ir and BrdU/NeuN cell density in the dentate gyrus, peak corticosterone levels, stereotypy scores |
| Topics | Neuroplasticity |
| Keywords | Cb1 receptor Hpa axis Periadolescent Sex difference Survival |
| Key findings | Adolescent HU-210 administration suppressed dentate gyrus BrdU-ir cell density and raised peak corticosterone responses to restraint stress in adult male but not female rats, while it increased amphetamine-induced stereotypy in adult females but not males. The authors argue these findings indicate sex-dependent, long-term changes to hippocampal structure and function following adolescent CB1 receptor activation. |
Abstract
Cannabinoid exposure during adolescence has adverse effects on neuroplasticity, emotional behavior, cognition, and reward sensitivity in adult rats. We investigated whether escalating doses of the cannabinoid receptor 1 (CB1 R) agonist, HU-210, in adolescence would affect adult hippocampal neurogenesis and behavioral processes putatively modulated by hippocampal neurogenesis, in adult male and female Sprague-Dawley rats. Escalating doses of HU-210 (25, 50, and 100 µg/kg), or vehicle were administered from postnatal day (PND) 35 to 46. Animals were left undisturbed until PND 70, when they were treated with 5-bromo-2-deoxyuridine (BrdU; 200 mg/kg) and perfused 21 days later to examine density of BrdU-ir and BrdU/NeuN cells in the dentate gyrus. In another cohort, hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute restraint stress (30 min; PND 75) and behavioral sensitization to d-amphetamine sulfate (1-2 mg/kg; PND 105-134) were assessed in adulthood. Adolescent HU-210 administration suppressed the density of BrdU-ir cells in the dentate gyrus in adult male, but not adult female rats. Adolescent HU-210 administration also induced significantly higher peak corticosterone levels and reminiscent of the changes in neurogenesis, this effect was more pronounced in adult males than females. However, adolescent cannabinoid treatment resulted in significantly higher stereotypy scores in adult female, but not male, rats. Thus, adolescent CB1 R activation suppressed hippocampal neurogenesis and increased stress responsivity in adult males, but not females, and enhanced amphetamine sensitization in adult female, but not male, rats. Taken together, increased CB1 R activation during adolescence results in sex-dependent, long-term, changes to hippocampal structure and function, an effect that may shed light on differing vulnerabilities to developing disorders following adolescent cannabinoid exposure, based on sex.
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 6
- Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review. Mol Med December 19, 2024
- Effects of psychedelics on neurogenesis and brain plasticity: A systematic review bioRxiv (Cold Spring Harbor Laboratory) July 20, 2023
- Δ9-Tetrahydrocannabinol Modulates Hippocampal Neurogenesis in Female Wistar Rats: Interaction with Estradiol. Neurochemical Research August 8, 2026
- Detrimental effects of adolescent escalating low-dose Δ9 -tetrahydrocannabinol leads to a specific bio-behavioural profile in adult male rats. British Journal of Pharmacology April 2021
- Evidence for the Risks and Consequences of Adolescent Cannabis Exposure. Journal of the American Academy of Child & Adolescent Psychiatry March 2017
and 1 more in the library
Cites 5
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- 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
- Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology October 2008
- Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proceedings of the National Academy of Sciences of the United States of America July 31, 2001