Endocannabinoid system: Potential novel targets for treatment of schizophrenia

NEUROBIOLOGY OF DISEASE

卷:53

Review

Saito, Atsushi^1,4  Ballinger, Michael D. L.¹  Pletnikov, Mikhail V.^1,2  Wong, Dean F.^1,2,3  Kamiya, Atsushi¹ 

[1] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Div Nucl Med, Baltimore, MD 21287 USA

[4] Dokkyo Med Univ, Sch Med, Dept Biol Psychiat & Neurosci, Mibu, Tochigi, Japan

关键词: Cannabis;    Endocannabinoid system;    Schizophrenia;    Genetic risk factor;    Environmental factor;   

DOI  :  10.1016/j.nbd.2012.11.020

来源: Elsevier

【 摘 要 】

Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free