The effect of social isolation on rat brain expression of genes associated with endocannabinoid signaling.
Rearing rats in single cages from weaning until adulthood (social isolation) produces a number of behavioral and neurochemical alterations similar to those observed in psychoses such as schizophrenia. Also, a dysregulation of the endocannabinoid system has been implicated in schizophrenia. The aim of this study was to examine the effect of social isolation on changes to mRNA expression of 1) the cannabinoid receptor CB(1), 2) enzymes responsible for the synthesis of the endocannabinoids anandamide (N-acyl phosphatidylethanolamine-phospholipase D or NAPE-PLD) and 2-arachidonoyl-glycerol or 2-AG (diacylglycerol lipase or DAGL isozymes alpha and beta) and 3) enzymes that degrade endocannabinoids (fatty acid amide hydrolase/FAAH for anandamide, and monoacylglycerol lipase/MAGL for 2-AG). Twenty-one-day post natal rats were randomly housed individually, or in groups of 6, for 8 weeks. CB(1) receptor, DAGL(alpha) and DAGLbeta, MAGL and FAAH mRNA levels were measured in the brains using in situ hybridization histochemistry. CB(1) receptor, DAGL(alpha), DAGLbeta, MAGL and NAPE-PLD mRNA expression levels were significantly higher in a number of brain regions from socially isolated rats; particularly in the prefrontal regions, cortical layers and a number of thalamic regions. DAGLbeta mRNA was significantly higher in the substantia nigra and ventral tegmental area. FAAH mRNA expression was significantly lower in a number of prefrontal regions, the cortical layers and in the caudate putamen and other associated areas of socially isolated rats. Such differences in endocannabinoid system mRNA in brains of socially isolated rats compared to normal rats further supports the potential importance of the endocannabinoid system in psychotic disease states.
Robinson
Stephanie A
SA
Drug Discovery Biology Laboratory, Department of Pharmacology and Monash Institute of Pharmaceutical Sciences, Monash University, Wellington Road, Clayton 3800, Victoria, Australia.
Loiacono
Richard E
RE
Christopoulos
Arthur
A
Sexton
Patrick M
PM
Malone
Daniel T
DT
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics*; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids