title: FAAH inhibition produces antidepressant-like efforts of mice to acute stress via synaptic long-term depression.
abstract: Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoid N-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits an in vivo long-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2. PF3845 significantly decreases passive behavioral coping of naïve mice to acute inescapable stress, which is also abolished by Tat-GluR2 peptide. However, PF3845 does not significantly affect sucrose assumption ratio of mice receiving chronic administration of corticosterone. These results suggest that FAAH inhibitors are able to produce antidepressant effects in naïve animals in response to acute stress through LTD at hippocampal glutamatergic CA3-CA1 synapses.
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; University of Ottawa Institute of Mental Health Research at the Royal, Departments of Psychiatry and Cellular & Molecular Medicine, Ottawa K1Z 7K4 Canada. Electronic address: fgx995@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: University of Ottawa Institute of Mental Health Research at the Royal, Departments of Psychiatry and Cellular & Molecular Medicine, Ottawa K1Z 7K4 Canada.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects; D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001095:Arachidonic Acids; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000517:prevention & control*; D063388:Endocannabinoids / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides; D011725:Pyridines / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D013315:Stress, Psychological / Q000517:prevention & control*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000928:Antidepressive Agents; D001095:Arachidonic Acids; D063388:Endocannabinoids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C557973:PF 3845; C078814:anandamide
keywords: AEA; Antidepressant; FAAH inhibitor; Hippocampus; LTD; Stress