Effects of Cannabinoid Agonists and Antagonists on Sleep in Laboratory Animals

Petrunich-Rutherford, Maureen L.; Calik, Michael W.

doi:10.1007/978-3-030-61663-2_7

Cited by 6 publications

(1 citation statement)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although CB1R-OX1R heterodimers have not previously been directly observed in animals, rodent studies in which cannabinoid and orexin compounds are co-administered have described unique physiological and behavioral outcomes based on (1) the receptor subtype targeted, and (2) separate versus combined compound treatments. Activating CBRs while blocking orexin receptors causes sedation or sleep-like effects ( Flores et al, 2016 ; Petrunich-Rutherford and Calik, 2021 ). In contrast, acutely activating both cannabinoid and orexin receptors increases appetite ( Mechoulam and Fride, 2001 ; Merroun et al, 2015 ) and reward sensitivity ( Plaza-Zabala et al, 2012 ; Flores et al, 2014 ; Yazdi et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

In vivo Evidence for Brain Region-Specific Molecular Interactions Between Cannabinoid and Orexin Receptors

et al. 2021

View full text Add to dashboard Cite

The endocannabinoid and orexin neuromodulatory systems serve key roles in many of the same biological functions such as sleep, appetite, pain processing, and emotional behaviors related to reward. The type 1 cannabinoid receptor (CB1R) and both subtypes of the orexin receptor, orexin receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) are not only expressed in the same brain regions modulating these functions, but physically interact as heterodimers in recombinant and neuronal cell cultures. In the current study, male and female C57BL/6 mice were co-treated with the cannabinoid receptor agonist CP55,940 and either the OX2R antagonist TCS-OX2-29 or the dual orexin receptor antagonist (DORA) TCS-1102. Mice were then evaluated for catalepsy, body temperature, thermal anti-nociception, and locomotion, after which their brains were collected for receptor colocalization analysis. Combined treatment with the DORA TCS-1102 and CP55,940 potentiated catalepsy more than CP55,940 alone, but this effect was not observed for changes in body temperature, nociception, locomotion, or via selective OX2R antagonism. Co-treatment with CP55,940 and TCS-1102 also led to increased CB1R-OX1R colocalization in the ventral striatum. This was not seen following co-treatment with TCS-OX2-29, nor in CB1R-OX2R colocalization. The magnitude of effects following co-treatment with CP55,940 and either the DORA or OX2R-selective antagonist was greater in males than females. These data show that CB1R-OX1R colocalization in the ventral striatum underlies cataleptic additivity between CP55,940 and the DORA TCS-1102. Moreover, cannabinoid-orexin receptor interactions are sex-specific with regards to brain region and functionality. Physical or molecular interactions between these two systems may provide valuable insight into drug-drug interactions between cannabinoid and orexin drugs for the treatment of insomnia, pain, and other disorders.

show abstract

Section: Introductionmentioning

confidence: 99%

In vivo Evidence for Brain Region-Specific Molecular Interactions Between Cannabinoid and Orexin Receptors

et al. 2021

View full text Add to dashboard Cite

show abstract

Approved cannabinoids for medical purposes – Comparative systematic review and meta-analysis for sleep and appetite

Spanagel

Bilbao

2021

Neuropharmacology

View full text Add to dashboard Cite

Systematic review/meta‐analysis on the role of CB1R regulation in sleep‐wake cycle in rats

Xue,

Xu,

Zhang

et al. 2024

J Evidence Based Medicine

View full text Add to dashboard Cite

ObjectiveA systematic review/meta‐analysis was conducted to investigate the effect of cannabinoid type‐1 receptor (CB1R) regulation on the sleep‐wake cycle of rats and to provide new ideas and evidence‐based basis for clinical research on the treatment of sleep disorders.MethodsWe searched Cochrane Library, PubMed, Web of Science, Embase, Chinese Biomedicine Literature Database (CBM), China National Knowledge Infrastructure, WanFang, and VIP databases for relevant papers, about the effects of CB1R agonists/antagonists on sleep‐wake cycle in rats, from inception to November 2023. Two reviewers performed study screening, data extraction, and risk of bias assessment using the SYRCLE's risk of bias tool. Meta‐analysis was performed using RevMan 5.3 software. Heterogeneity test was performed on the included studies (Test standard α = 0.1). I2 value was used to evaluate the heterogeneity. Forest plot was drawn, and p ≤ 0.05 indicates statistically significant difference.ResultsA total of 16 trials involving 484 experimental rats were included. The methodological quality evaluation results showed that the overall quality of the included studies was low. The results of the meta‐analysis showed that single administration of CB1R agonists could shorten the wakefulness (W) time in the first 6 h (h) (standardized mean difference (SMD) = –2.52, 95% confidence interval (CI) (–3.83, –1.22), p = 0.0002) and 24 h (SMD = –0.84, 95% CI (–1.31, –0.36), p = 0.0005) after administration, prolong nonrapid eye movement sleep (NREM) time (SMD = 1.75, 95% CI (0.54, 2.95), p = 0.005) and rapid eye movement sleep (REM) time (SMD = 1.76, 95% CI (0.26, 3.26), p = 0.02), and increase REM frequency after administration (SMD = 1.67, 95% CI (0.98, 2.35), p < 0.00001), these results were all statistically different. There were no significant differences in sleep latency and average duration of REM. Single administration of CB1R antagonists prolonged the first 6 h W time after administration (SMD = 1.36, 95%CI (0.29, 2.43), p = 0.01), shortened the first 6 h NREM time (SMD = –1.73, 95% CI (–2.88, –0.57), p = 0.003) and REM time (SMD = –2.07, 95% CI (–3.17, –0.96), p = 0.0003) after administration, and increased the frequency of W after administration (SMD = 3.57, 95% CI (1.42, 5.72), p = 0.001). There was no statistical difference in the average duration of W. REM time and REM frequency increased after continuous CB1R agonist withdrawal.ConclusionsAccording to the existing evidence, CB1R played a pivotal role in regulating the sleep‐wake cycle in rats. CB1R agonists tended to reduce W time, increase NREM and REM sleep times, boost REM frequency, and promote sleep. Conversely, CB1R antagonists could increase the duration and frequency of W, shorten NREM and REM sleep times, and promote W.

show abstract

Effects of Cannabinoid Agonists and Antagonists on Sleep in Laboratory Animals

Cited by 6 publications

References 118 publications

In vivo Evidence for Brain Region-Specific Molecular Interactions Between Cannabinoid and Orexin Receptors

In vivo Evidence for Brain Region-Specific Molecular Interactions Between Cannabinoid and Orexin Receptors

Approved cannabinoids for medical purposes – Comparative systematic review and meta-analysis for sleep and appetite

Systematic review/meta‐analysis on the role of CB1R regulation in sleep‐wake cycle in rats

Contact Info

Product

Resources

About