Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.
Lindsay Silva, Rita Black, Michael Michaelides, Yasmin L. Hurd, Diana Dow-Edwards
Neurotoxicology and Teratology 2016 DOI: 10.1016/j.ntt.2016.02.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Adolescent male and female rats, either shipped from a supplier or born in the vivarium, dosed during postnatal days 29-38, with additional groups dosed pre-puberty (females P21-30) and during puberty (males P39-48) |
| Dose | 3 mg/kg |
| Duration | Once daily injections during postnatal days 29-38; additional groups dosed P21-30 (females) or P39-48 (males) |
| Measures | Elevated plus maze (EPM), forced swim test (FST), acoustic startle habituation, pre-pulse inhibition, plasma corticosterone, cannabinoid receptor 1 (CB1R) mRNA expression, CP55,940 stimulated [35S]GTPγS binding |
| Topics | Cannabis |
| Keywords | Cb1 receptor expression Corticosterone Delta-9-tetrahydrocannabinol Emotionality Puberty Sex differences |
| Key findings | Male adolescent rats were more sensitive than females to THC's anxiolytic and antidepressant-like effects, while early shipping stress enhanced THC responses in both sexes on different measures. THC increased CB1 receptor mRNA and tended to decrease CP55,940-stimulated binding in the central amygdala of females only, and rats treated just before puberty showed reduced anxiety that was not seen in those treated during puberty. |
Abstract
Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Effects of Chronic Exposure to Low-Dose delta-9-Tetrahydrocannabinol in Adolescence and Adulthood on Serotonin/Norepinephrine Neurotransmission and Emotional Behavior The International Journal of Neuropsychopharmacology July 23, 2020
- Sex-specific vulnerabilities in cannabis-induced psychosis: A scoping review. Asian Journal of Psychiatry July 8, 2026
- Divergent outcomes of delta 9 - tetrahydrocannabinol (THC) in adolescence on mesocortical dopamine and cognitive development in male and female mice. Psychopharmacology October 2025
- Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 13, 2025
and 10 more in the library
Cites 6
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat. Neuroscience Letters August 18, 2015
- Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology 2011
- Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology October 2008
- Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addiction Biology June 2008
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