Differential effects of the antidepressants tranylcypromine and fluoxetine on limbic cannabinoid receptor binding and endocannabinoid contents.
The goal of this study was to determine whether the endocannabinoid system is altered by chronic antidepressant treatment. The effects of 3-week administration of the monoamine oxidase inhibitor, tranylcypromine (10 mg/kg) and the selective serotonin reuptake inhibitor, fluoxetine (5 mg/kg) on cannabinoid CB(1) receptor densities and endocannabinoid contents were determined in limbic brain regions of the rat. Tranylcypromine significantly reduced tissue content of the endocannabinoid N-arachidonylethanolamine (anandamide) in the prefrontal cortex, hippocampus and hypothalamus and increased 2-arachidonoylglycerol content in the prefrontal cortex. Tranylcypromine treatment significantly increased CB(1) receptor binding density in the prefrontal cortex and hippocampus, but not in the hypothalamus. Treatment with fluoxetine increased CB(1) receptor density in the prefrontal cortex, but had no effect on endocannabinoid contents in any brain region examined. These data suggest that monoaminergic neurotransmission can regulate the endocannabinoid system and further indicates a role of the endocannabinoid system in affective illness and its treatment.
Hill
Matthew N
MN
Department of Psychology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada. mhill_psych_ubc@hotmail.com
Ho
Wing-Sze Vanessa
WS
Hillard
Cecilia J
CJ
Gorzalka
Boris B
BB
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D063388:Endocannabinoids; D005473:Fluoxetine / Q000494:pharmacology*; D005989:Glycerides / Q000378:metabolism; D008024:Ligands; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014191:Tranylcypromine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; D001095:Arachidonic Acids; D015306:Biogenic Monoamines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005473:Fluoxetine; D005989:Glycerides; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D017367:Selective Serotonin Reuptake Inhibitors; D014191:Tranylcypromine; C094503:glyceryl 2-arachidonate; C078814:anandamide