Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.
Michael D Ballinger, Atsushi Saito, Bagrat Abazyan, Yu Taniguchi, Ching-Hsun Huang, Koki Ito, Xiaolei Zhu, Hadar Segal, Hanna Jaaro-Peled, Akira Sawa, Ken Mackie, Mikhail V Pletnikov, Atsushi Kamiya
Neurobiology of Disease October 2015 DOI: 10.1016/j.nbd.2015.06.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice expressing a dominant-negative mutant of DISC1 (DN-DISC1) and wild-type mice |
| Intervention | Delta-9-tetrahydrocannabinol (Δ(9)-THC) |
| Duration | Chronic adolescent treatment |
| Topics | Cannabis |
| Keywords | Adolescent development Chronic cannabis use Disc1 Fear memory Gene–environment interaction |
| Key findings | Chronic adolescent THC treatment worsened fear-associated memory deficits in adult DN-DISC1 mice, and both the DISC1 mutation and adolescent THC reduced CB1R expression in the prefrontal cortex, hippocampus, and amygdala. Context-dependent fear memory retrieval evoked less c-Fos in these regions in DN-DISC1 mice, and cue-dependent retrieval showed a synergistic c-Fos reduction in DN-DISC1 mice exposed to THC. The authors suggest altered CB1R-mediated signaling may underlie susceptibility to adolescent cannabis effects. |
Abstract
Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental illnesses before full-onset in early adulthood, it is particularly important to investigate how genetic insults and adolescent cannabis exposure interact to affect brain development and function. Here we show for the first time that a perturbation in disrupted in schizophrenia 1 (DISC1) exacerbates the response to adolescent exposure to delta-9-tetrahydrocannabinol (Δ(9)-THC), a major psychoactive ingredient of cannabis, consistent with the concept that gene-environment interaction may contribute to the pathophysiology of psychiatric conditions. We found that chronic adolescent treatment with Δ(9)-THC exacerbates deficits in fear-associated memory in adult mice that express a putative dominant-negative mutant of DISC1 (DN-DISC1). Synaptic expression of cannabinoid receptor 1 (CB1R) is down-regulated in the prefrontal cortex, hippocampus, and amygdala, critical brain regions for fear-associated memory, by either expression of DN-DISC1 or adolescent Δ(9)-THC treatment. Notably, elevation of c-Fos expression evoked by context-dependent fear memory retrieval is impaired in these brain regions in DN-DISC1 mice. We also found a synergistic reduction of c-Fos expression induced by cue-dependent fear memory retrieval in DN-DISC1 with adolescent Δ(9)-THC exposure. These results suggest that alteration of CB1R-mediated signaling in DN-DISC1 mice may underlie susceptibility to detrimental effects of adolescent cannabis exposure on adult behaviors.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 4
- The Role of Cannabis in the Development of Psychosis. Turk psikiyatri dergisi = Turkish journal of psychiatry 2024
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
- Concomitant THC and stress adolescent exposure induces impaired fear extinction and related neurobiological changes in adulthood. Neuropharmacology January 2019
- Adolescent Δ9-Tetrahydrocannabinol Exposure and Astrocyte-Specific Genetic Vulnerability Converge on Nuclear Factor-κB-Cyclooxygenase-2 Signaling to Impair Memory in Adulthood. Biological Psychiatry August 16, 2018
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