Deletion of Cryab increases the vulnerability of mice to the addiction-like effects of the cannabinoid JWH-018 via upregulation of striatal NF-κB expression
Leandro Val Sayson, Darlene Mae Ortiz, Hyun Jun Lee, Mikyung Kim, Raly James Perez Custodio, Jaesuk Yun, Chae Hyeon Lee, Yong Sup Lee, Hye Jin, Jae Hoon Cheong, Hee Jin Kim
Frontiers in Pharmacology March 16, 2023 DOI: 10.3389/fphar.2023.1135929 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Cryab knockout and wild-type mice |
| Intervention | JWH-018 |
| Topics | Addiction Neuroplasticity |
| Keywords | Conditioned place preference Neuroinflammation Endocannabinoid system Cannabinoid receptor Delta-9-tetrahydrocannabinol Pharmacology Knockout mouse Synthetic cannabinoids Dopamine transporter Downregulation and upregulation Antagonist Biochemistry Dopaminergic |
| Citations | 4 |
| Key points | Cryab knockout mice exhibit greater cannabinoid-induced self-administration and place preference, along with increased neuroinflammation via NF-κB, which may mediate enhanced addiction-like responses to cannabinoids. |
Abstract
Synthetic cannabinoids have exhibited unpredictable abuse liabilities, especially self-administration (SA) responses in normal rodent models, despite seemingly inducing addiction-like effects in humans. Thus, an efficient pre-clinical model must be developed to determine cannabinoid abuse potential in animals and describe the mechanism that may mediate cannabinoid sensitivity. The Cryab knockout (KO) mice were recently discovered to be potentially sensitive to the addictive effects of psychoactive drugs. Herein, we examined the responses of Cryab KO mice to JWH-018 using SA, conditioned place preference, and electroencephalography. Additionally, the effects of repeated JWH-018 exposure on endocannabinoid- and dopamine-related genes in various addiction-associated brain regions were examined, along with protein expressions involving neuroinflammation and synaptic plasticity. Cryab KO mice exhibited greater cannabinoid-induced SA responses and place preference, along with divergent gamma wave alterations, compared to wild-type (WT) mice, implying their higher sensitivity to cannabinoids. Endocannabinoid- or dopamine-related mRNA expressions and accumbal dopamine concentrations after repeated JWH-018 exposure were not significantly different between the WT and Cryab KO mice. Further analyses revealed that repeated JWH-018 administration led to possibly greater neuroinflammation in Cryab KO mice, which may arise from upregulated NF-κB, accompanied by higher expressions of synaptic plasticity markers, which might have contributed to the development of cannabinoid addiction-related behavior in Cryab KO mice. These findings signify that increased neuroinflammation via NF-κB may mediate the enhanced addiction-like responses of Cryab KO mice to cannabinoids. Altogether, Cryab KO mice may be a potential model for cannabinoid abuse susceptibility.
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| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Mice | 2023 | Computational docking and experimental validation | |
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study |
Citations in the library
Cites 6
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- 25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential Addiction Biology November 1, 2020
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- Δ9-THC exposure attenuates aversive effects and reveals appetitive effects of K2/'Spice' constituent JWH-018 in mice. Behavioural Pharmacology June 2014
- The effect of chronic cannabinoids on broadband EEG neural oscillations in humans. Neuropsychopharmacology September 2012
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