Ovarian hormones and chronic administration during adolescence modify the discriminative stimulus effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) in adult female rats.
Peter J Winsauer, Catalin M Filipeanu, Evangeline M Bailey, Jerielle L Hulst, Jessie L Sutton
Pharmacology, Biochemistry, and Behavior September 2012 DOI: 10.1016/j.pbb.2012.06.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Population | Female rats, either gonadally intact or ovariectomized, treated during adolescence |
| Intervention | Delta-9-tetrahydrocannabinol (Δ⁹-THC) |
| Dose | 5.6 mg/kg daily during adolescence; training and substitution doses of 0.32-3.2 mg/kg |
| Duration | 40 daily intraperitoneal injections during adolescence |
| Topics | Cannabis |
| Key findings | Ovariectomized female rats showed higher THC-lever responding at lower THC doses than intact rats, and the ovariectomized THC-treated group was less sensitive to THC's rate-decreasing effects. Chronic adolescent THC decreased striatal CB1 receptor levels and hippocampal p-CREB in both ovariectomized and intact females, while selectively increasing striatal p-CREB in the ovariectomized saline group. The authors suggest these data indicate adolescent cannabinoid exposure could alter adult responsiveness in human females. |
Abstract
Marijuana abuse during adolescence may alter its abuse liability during adulthood by modifying the interoceptive (discriminative) stimuli produced, especially in females due to an interaction with ovarian hormones. To examine this possibility, either gonadally intact or ovariectomized (OVX) female rats received 40 intraperitoneal injections of saline or 5.6 mg/kg of Δ⁹-THC daily during adolescence, yielding 4 experimental groups (intact/saline, intact/Δ⁹-THC, OVX/saline, and OVX/Δ⁹-THC). These groups were then trained to discriminate Δ⁹-THC (0.32-3.2 mg/kg) from saline under a fixed-ratio (FR) 20 schedule of food presentation. After a training dose was established for the subjects in each group, varying doses of Δ⁹-THC were substituted for the training dose to obtain dose-effect (generalization) curves for drug-lever responding and response rate. The results showed that: 1) the OVX/saline group had a substantially higher mean response rate under control conditions than the other three groups, 2) both OVX groups had higher percentages of THC-lever responding than the intact groups at doses of Δ⁹-THC lower than the training dose, and 3) the OVX/Δ⁹-THC group was significantly less sensitive to the rate-decreasing effects of Δ⁹-THC compared to other groups. Furthermore, at sacrifice, western blot analyses indicated that chronic Δ⁹-THC in OVX and intact females decreased cannabinoid type-1 receptor (CB1R) levels in the striatum, and decreased phosphorylation of cyclic adenosine monophosphate response element binding protein (p-CREB) in the hippocampus. In contrast to the hippocampus, chronic Δ⁹-THC selectively increased p-CREB in the OVX/saline group in the striatum. Extracellular signal-regulated kinase (ERK) was not significantly affected by either hormone status or chronic Δ⁹-THC. In summary, these data in female rats suggest that cannabinoid abuse by adolescent human females could alter their subsequent responsiveness to cannabinoids as adults and have serious consequences for brain development.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 5
- Sex and Gender Differences in the Effects of Novel Psychoactive Substances. Brain Sciences September 3, 2020
- 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
- Evaluation of cannabimimetic effects of selected minor cannabinoids and Terpenoids in mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry June 8, 2024
- Δ9-tetrahydrocannabinol: Drug discrimination abuse liability testing in female Lister Hooded rats: Trials, tribulations and triumphs. Journal of pharmacological and toxicological methods 2020
- Comparison of the discriminative stimulus and response rate effects of Δ9-tetrahydrocannabinol and synthetic cannabinoids in female and male rats. Drug and Alcohol Dependence March 1, 2017
Cites 11
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