Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood.
Rocio Saravia, Marc Ten-Blanco, Marina Julià-Hernández, Humberto Gagliano, Raül Andero, Antonio Armario, Rafaël Maldonado, Fernando Berrendero
Neuropharmacology January 2019 DOI: 10.1016/j.neuropharm.2018.11.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Adolescent mice |
| Interventions | Δ9-tetrahydrocannabinol (THC) stress |
| Topics | Cannabis |
| Keywords | Adolescence Amygdala Dendritic spines Fear extinction Stress Δ9-tetrahydrocannabinol |
| Key findings | Adolescent mice given both THC and stress showed impaired cued fear extinction in adulthood, while those exposed to either factor alone did not. This extinction resistance was linked to reduced neuronal activity in the basolateral amygdala and infralimbic prefrontal cortex, more immature dendritic spines in the basolateral amygdala, and elevated corticosterone after fear conditioning. The authors propose that combined adolescent cannabis exposure and stress may lead to long-term anxiety disorders characterized by pathological fear. |
Abstract
Δ9-tetrahydrocannabinol (THC) consumption during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. The interaction between genetic or environmental events and cannabinoid exposure in the adolescent period can also contribute to exacerbate behavioural deficits in adulthood. Here we investigate the effects of THC treatment as well as the consequences of concomitant THC and stress exposure during adolescence in the extinction of fear memory in adult mice. Adolescent mice treated with THC and exposed to stress exhibit impaired cued fear extinction in adulthood. However, no effect was observed in animals exposed to these two factors separately. Notably, resistance to fear extinction was associated with decreased neuronal activity in the basolateral amygdala (BLA) and the infralimbic prefrontal cortex, suggesting a long-term dysregulation of the fear circuit. These changes in neuronal activation were paralleled with structural plasticity alterations. Indeed, an increase of immature dendritic spines in pyramidal neurons of the BLA was revealed in mice simultaneously exposed to THC and stress. Corticosterone levels were also enhanced after the cued fear conditioning session in the same experimental group. These results show that an interaction between cannabis exposure and stress during adolescence may lead to long-term anxiety disorders characterized by the presence of pathological fear.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 8
- Chronic adolescent exposure to cannabis in mice leads to sex-biased changes in gene expression networks across brain regions Neuropsychopharmacology August 22, 2022
- An Update on the Behavioral and Neurobiological Effects of Cannabis Use in Adolescents: A Translational Perspective. American Journal of Psychiatry July 1, 2025
- THC and CBD: Similarities and differences between siblings. Neuron February 1, 2023
- Cannabinoid use is enhanced by stress and changes conditioned stress responses. Neuropsychopharmacology April 2022
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
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