title: A dual inhibitor of FAAH and TRPV1 channels shows dose-dependent effect on depression-like behaviour in rats.
abstract: OBJECTIVE
  The cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are proposed to mediate opposite behavioural responses. Their common denominator is the endocannabinoid ligand anandamide (AEA), which is believed to mediate antidepressant-like effect via CB1-R stimulation and depressive-like effect via TRPV1 activation. This is supposed to explain the bell-shaped dose-response curve for anandamide in preclinical models.
  
  
  METHODS
  We investigated this assumption by administering the dual inhibitor of AEA hydrolysis and TRPV1 activation N-arachidonoyl-serotonin (AA-5HT) into the medial prefrontal cortex of rats. AA-5HT was given in three different doses (0.125, 0.250, 0.500 nmol/0.4 µl/side) and rat behaviour was assessed in the forced swim test.
  
  
  RESULTS
  Our results show significant antidepressant-like effect of AA-5HT (0.250 nmol) but no effects of low or high doses. The effect of 0.250 nmol AA-5HT was partially attenuated when coadministering the inverse CB1-agonist rimonabant (1.6 µg).
  
  
  CONCLUSIONS
  A 0.250 nmol of AA-5HT administration into the medial prefrontal cortex induced a significant antidepressant-like effect that was partially attenuated by locally blocking CB1-receptor.
authors.affiliation: 1Translational Neuropsychiatry Unit,Departments of Clinical Medicine,Aarhus University,RisskovDenmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Kirkedal
authors.affiliation: 1Translational Neuropsychiatry Unit,Departments of Clinical Medicine,Aarhus University,RisskovDenmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: 3Departament of Pharmacology,Federal University of Minas Gerais,MG,Brazil.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Moreira
authors.affiliation: 1Translational Neuropsychiatry Unit,Departments of Clinical Medicine,Aarhus University,RisskovDenmark.
authors.forename: Sâmia Regiane Lourenco
authors.initials: SRL
authors.lastname: Joca
authors.affiliation: 1Translational Neuropsychiatry Unit,Departments of Clinical Medicine,Aarhus University,RisskovDenmark.
authors.forename: Nico
authors.initials: N
authors.lastname: Liebenberg
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage; D003863:Depression; D004305:Dose-Response Relationship, Drug; D054314:Drug Inverse Agonism; D008297:Male; D010880:Piperidines / Q000008:administration & dosage; D017397:Prefrontal Cortex / Q000187:drug effects*; D011720:Pyrazoles / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000928:Antidepressive Agents; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant; D012701:Serotonin; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C493922:Trpv1 protein, rat; C114007:arachidonoylserotonin
keywords: cannabinoid receptor 1; fatty acid amide hydrolase; forced swim test; medial prefrontal cortex; trans potential vanilloid receptor 1