Electroconvulsive shock treatment differentially modulates cortical and subcortical endocannabinoid activity.
Previous studies indicate that the endocannabinoid system is a potential target for the treatment of depression. To further examine this question we assessed the effects of electroconvulsive shock (ECS) treatment, both a single session and 10 daily sessions, on endocannabinoid content, CB(1) receptor binding parameters and CB(1) receptor-mediated [(35)S]GTPgammaS binding in the prefrontal cortex, hippocampus, hypothalamus and amygdala. A single ECS session resulted in a general reduction in the binding affinity of the CB(1) receptor in all brain regions examined, as well as reductions in N-arachidonylethanolamine (anandamide) content in the prefrontal cortex and the hippocampus, reduced hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) in the prefrontal cortex and an increase in the binding site density of the CB(1) receptor in the amygdala. Following 10 ECS sessions, all these effects subsided except for the reductions in anandamide content in the prefrontal cortex, which increased in magnitude, as well as the reductions in FAAH activity in the prefrontal cortex. Additionally, repeated ECS treatment resulted in a significant reduction in the binding site density of the CB(1) receptor in the prefrontal cortex, but did not alter CB(1) receptor-mediated [(35)S]GTPgammaS binding. Repeated ECS treatment also significantly enhanced the sensitivity of CB(1) receptor-mediated [(35)S]GTPgammaS binding in the amygdala. Collectively, these data demonstrate that ECS treatment results in a down-regulation of cortical and an up-regulation of subcortical endocannabinoid activity, illustrating the possibility that the role of the endocannabinoid system in affective illness may be both complex and regionally specific.
Hill
Matthew N
MN
Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada.
Barr
Alasdair M
AM
Ho
W-S Vanessa
WS
Carrier
Erica J
EJ
Gorzalka
Boris B
BB
Hillard
Cecilia J
CJ
D000581:Amidohydrolases / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001665:Binding Sites; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D015536:Down-Regulation; D004597:Electroshock; D063388:Endocannabinoids; D004789:Enzyme Activation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015854:Up-Regulation; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide