title: Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear.
abstract: Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders.
authors.affiliation: Center for the Study of Traumatic Stress, Dept. of Psychiatry, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. kwang.choi@usuhs.edu
authors.forename: Kwang
authors.initials: K
authors.lastname: Choi
authors.forename: Thien
authors.initials: T
authors.lastname: Le
authors.forename: Jennifer
authors.initials: J
authors.lastname: McGuire
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xing
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Clarissa C
authors.initials: CC
authors.lastname: Parker
authors.forename: Luke R
authors.initials: LR
authors.lastname: Johnson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ursano
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003214:Conditioning, Classical / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008124:Locomotion / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019964:Mood Disorders / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics*; D055815:Young Adult
chemical_list: C469526:Cnr2 protein, rat; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid