Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats

Zamberletti, Erica; Gabaglio, Marina; Prini, Pamela; Rubino, Tiziana; Parolaro, Daniela

doi:10.1016/j.euroneuro.2015.09.021

Cited by 87 publications

(80 citation statements)

References 34 publications

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“…Cannabis users had more cerebellar grey matter volume compared to non-users, but this was not associated with depressive symptoms [133]. Preclinical studies have indicated that adolescent THC exposure elevates depressive-like behavior in adulthood in female rats [61, 164] but not male rats [61]. Cannabinoid exposure in males, in contrast, has been shown to decrease depressive-like behavior [149, 165].…”

Section: Sex Differences In Cannabis Use Comorbidity With Psychiatricmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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Purpose of the Review Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Recent Findings Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. Summary As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.

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Section: Sex Differences In Cannabis Use Comorbidity With Psychiatricmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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“…13 For detailed information, see Appen dix 1, available at jpn.ca/170082a1. Behavioural data were expressed as means ± standard errors of the mean (SEM) and analyzed using 2way analysis of variance (ANOVA) fol lowed by a Tukey multiple comparison post hoc test.…”

Section: Behavioural Testmentioning

confidence: 99%

“…Because the onset of the depressive/psychoticlike pheno type is restricted to adolescent THC exposure, [8][9][10][11][12][13][14] we investi gated whether described alterations in histone modifications and gene expression were restricted to the adolescent treat ment. We performed the same protocol of injections (Fig.…”

Section: Adult V Adolescent Thc Exposure Differentially Affects Histmentioning

confidence: 99%

“…To investigate the possible role of H3K9me3 increase induced by adolescent THC exposure, [8][9][10][11][12][13] we administered chaetocin, an inhibitor of the HMTs SUV39H1 and G9a, 34,35 simultane ously with THC treatment. To establish the active dose of chaetocin in vivo, we first tested 2 different intraperitoneal doses (0.05 mg/kg and 0.1 mg/kg), and 24 hours after the in jection, we investigated H3K9me3 levels.…”

Section: Chaetocin-induced H3k9me3 Inhibition During Adolescent Thc Ementioning

confidence: 99%

“…[5][6][7] We have shown previously that chronic admin istration of Δ9tetrahydrocannabinol (THC), the psychoactive ingredient of cannabis, in adolescent but not adult female rats induces behavioural and biochemical signs relevant for de pression and psychosis [8][9][10][11][12][13] later in life. Interestingly, long term effects of THC seem to be sexspecific.…”

Section: Introductionmentioning

confidence: 99%

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Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

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Rusconi

Zamberletti

et al. 2018

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In Vivo Imaging of Translocator Protein in Long-term Cannabis Users

et al. 2019

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IMPORTANCE Cannabis is the most commonly used illicit drug in the world. Cannabinoids have been shown to modulate immune responses; however, the association of cannabis with neuroimmune function has never been investigated in vivo in the human brain.OBJECTIVE To investigate neuroimmune activation or 18-kDa translocator protein (TSPO) levels in long-term cannabis users, and to evaluate the association of brain TSPO levels with behavioral measures and inflammatory blood biomarkers. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study based in Toronto, Ontario, recruited individuals from January 1, 2015, to October 30, 2018. Participants included long-term cannabis users (n = 24) and non-cannabis-using controls (n = 27). Cannabis users were included if they had a positive urine drug screen for only cannabis and if they used cannabis at least 4 times per week for the past 12 months and/or met the criteria for cannabis use disorder. All participants underwent a positron emission tomography scan with [ 18 F]FEPPA, or fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl) acetamide.MAIN OUTCOMES AND MEASURES Total distribution volume was quantified across regions of interest. Stress and anxiety as well as peripheral measures of inflammatory cytokines and C-reactive protein levels were also measured. RESULTSIn total, 24 long-term cannabis users (mean [SD] age, 23.1 [3.8] years; 15 men [63%]) and 27 non-cannabis-using controls (mean [SD] age, 23.6 [4.2] years; 18 women [67%]) were included and completed all study procedures. Compared with the controls, cannabis users had higher [ 18 F]FEPPA total distribution volume (main group effect: F 1,48 = 6.5 [P = .01]; ROI effect: F 1,200 = 28.4 [P < .001]; Cohen d = 0.6; 23.3% higher), with a more prominent implication for the cannabis use disorder subgroup (n = 15; main group effect: F 1,39 = 8.5 [P = .006]; ROI effect: F 1,164 = 19.3 [P < .001]; Cohen d = 0.8; 31.5% higher). Greater TSPO levels in the brain were associated with stress and anxiety and with higher circulating C-reactive protein levels in cannabis users. CONCLUSIONS AND RELEVANCEThe results of this study suggest that TSPO levels in cannabis users, particularly in those with cannabis use disorder, are higher than those in non-cannabis-using controls. The findings emphasize the need for more complementary preclinical systems for a better understanding of the role of cannabinoids and TSPO in neuroimmune signaling.

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Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats

Cited by 87 publications

References 34 publications

Mechanisms Underlying Sex Differences in Cannabis Use

Mechanisms Underlying Sex Differences in Cannabis Use

Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

In Vivo Imaging of Translocator Protein in Long-term Cannabis Users

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