title: Hippocampal endocannabinoids play an important role in induction of long-term potentiation and regulation of contextual fear memory formation.
abstract: Recent studies show contradictory results regarding the contribution of endocannabinoids in fear memory formation and long-term synaptic plasticity. In this study, we investigated the effects of both cannabinoid receptor type 1 (CB1 receptor) antagonist AM281 and anandamide reuptake inhibitor AM404 on the formation of contextual fear memory in adult mice. Both i.p. and intra-hippocampal injections of AM281 promoted contextual fear memory while a high dose of AM404 inhibited it. These findings demonstrate that CB1 receptor-mediated signaling negatively contributes to contextual fear memory formation. We further investigated the induction of long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices and found that AM281 impaired the induction of LTP. Additionally, the blockade of LTP by AM281 was completely prevented by bath application of picrotoxin, a selective antagonist of GABA(A) receptor. Taken together, these results indicate that activation of CB1 receptor contributes to induction of LTP via a GABA(A) receptor-mediated mechanism.
authors.affiliation: School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
authors.forename: Qing-Shu
authors.initials: QS
authors.lastname: Lin
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Dang
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Jieyan
authors.initials: J
authors.lastname: Chen
authors.forename: Sheng-Tian
authors.initials: ST
authors.lastname: Li
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005239:Fear / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018756:GABA Antagonists; D009025:Morpholines; D010852:Picrotoxin; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; C109925:AM 281; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide