Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior
Autor: | Aurora Bonvino, Rita Masellis, Leonardo Fazio, Marco Colizzi, Alessandro Bertolino, Laura Ferranti, Daniela Marvulli, Gianluca Ursini, Giuseppe Blasi, Annamaria Porcelli |
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Rok vydání: | 2014 |
Předmět: |
Male
Alcohol Drinking Genotype medicine.medical_treatment Receptor expression Messenger Prefrontal Cortex Marijuana Smoking Polymorphism Single Nucleotide Tobacco Use Receptor Cannabinoid CB1 Memory Functional neuroimaging medicine Humans RNA Messenger Polymorphism Prefrontal cortex Cannabinoid Effects of cannabis Pharmacology medicine.diagnostic_test biology Working memory Functional Neuroimaging Female Genetic Variation Magnetic Resonance Imaging Memory Short-Term Single Nucleotide biology.organism_classification CB1 Psychiatry and Mental health Short-Term RNA Original Article Cannabis Functional magnetic resonance imaging Psychology Neuroscience Receptor |
Zdroj: | Colizzi, M, Fazio, L, Ferranti, L, Porcelli, A, Masellis, R, Marvulli, D, Bonvino, A, Ursini, G, Blasi, G & Bertolino, A 2015, ' Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior ', Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, vol. 40, no. 3, pp. 640-9 . https://doi.org/10.1038/npp.2014.213 |
ISSN: | 1740-634X 0893-133X |
Popis: | Cannabinoid signaling is involved in different brain functions and it is mediated by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous evidence suggests an association between cognition and cannabis use. The logical interaction between genetically determined cannabinoid signaling and cannabis use has not been determined. Therefore, we investigated whether CNR1 variation predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue. Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the relevant functional SNP and were evaluated for cannabis use by the Cannabis Experience Questionnaire. All individuals performed the 2-back working memory task during functional magnetic resonance imaging. CNR1 rs1406977 was associated with prefrontal mRNA and individuals carrying a G allele had reduced CNR1 prefrontal mRNA levels compared with AA subjects. Moreover, functional connectivity MRI demonstrated that G carriers who were also cannabis users had greater functional connectivity in the left ventrolateral prefrontal cortex and reduced working memory behavioral accuracy during the 2-back task compared with the other groups. Overall, our results indicate that the deleterious effects of cannabis use are more evident on a specific genetic background related to its receptor expression. |
Databáze: | OpenAIRE |
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