Escalating low-dose Δ9 -tetrahydrocannabinol exposure during adolescence induces differential behavioral and neurochemical effects in male and female adult rats.
Nafsika Poulia, Foteini Delis, Charalampos Brakatselos, Panagiotis Lekkas, Nikolaos Kokras, Christina Dalla, Katerina Antoniou
European Journal of Neuroscience July 2020 DOI: 10.1111/ejn.14598 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study in rats (preclinical animal study) Peer reviewed |
|---|---|
| Population | Adult male and female rats exposed to escalating low-dose Δ9-THC during adolescence |
| Intervention | Δ9-tetrahydrocannabinol (Δ9-THC) |
| Dose | escalating low doses |
| Topics | Cannabis |
| Keywords | Adult Behavioral analysis Cannabinoids Neuronal plasticity |
| Key findings | Adolescent escalating low-dose Δ9-THC exposure produced long-term, sex-specific behavioral and neurobiological changes in adult rats. Males showed increased locomotor activity, impaired motor habituation, and short-term spatial memory deficits with decreased prefrontal BDNF and altered serotonergic markers; females showed reduced vertical activity and spatial memory deficits with increased prefrontal BDNF. The authors suggest these changes may relate to sex-differentiated psychopathology risk. |
Abstract
Cannabinoid administration during adolescence affects various physiological processes, such as motor and affective response, cognitive-related functions and modulates neurotransmitter activity. Literature remains scant concerning the parallel examination of the effects of adolescent escalating low-dose Δ9 -tetrahydrocannabinol (Δ9 -THC) on the behavioral and plasticity profile of adult rats in both sexes. Herein, we investigated the long-term behavioral, neurochemical and neurobiological effects of adolescent escalating low Δ9 -THC doses in adult male and female rats. In adult males, adolescent low-dose Δ9 -THC exposure led to increased spontaneous locomotor activity, impaired behavioral motor habituation and defective short-term spatial memory, paralleled with decreased BDNF protein levels in the prefrontal cortex. In this brain area, serotonergic activity was increased, as depicted by the increased serotonin turnover rate, while the opposite effect was observed in the hippocampus, a region where SERT levels were enhanced by Δ9 -THC, compared with vehicle. In adult females, adolescent Δ9 -THC treatment led to decreased spontaneous vertical activity and impaired short-term spatial memory, accompanied by increased BDNF protein levels in the prefrontal cortex. Present findings emphasize the key role of adolescent escalating low Δ9 -THC exposure in the long-term regulation of motor response, spatial-related cognitive functions and neuroplasticity indices in adulthood. In this framework, these changes could, at a translational level, contribute to clinical issues suggesting the development of psychopathology in a sex-differentiated manner following Δ9 -THC exposure during adolescence.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 11
- 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
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie February 1, 2025
- 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
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Cites 10
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