title: NMDA and D1 receptors are involved in one-trial tolerance to the anxiolytic-like effects of diazepam in the elevated plus maze test in rats.
abstract: The elevated plus maze (EPM) test is used to examine anxiety-like behaviors in rodents. One interesting phenomenon in the EPM test is one-trial tolerance (OTT), which refers to the reduction in the anxiolytic-like effects of benzodiazepines when rodents are re-exposed to the EPM. However, the underlying mechanism of OTT is still unclear. In this study, we reported that OTT occurred when re-exposure to the EPM (trial 2) only depended on the prior experience of the EPM (trial 1) rather than diazepam treatment. This process was memory-dependent, as it was prevented by the N-methyl-D-aspartate (NMDA) receptors antagonist MK-801 1.5h before trial 2. In addition, OTT was maintained for at least one week but was partially abolished after an interval of 28 days. Furthermore, the administration of the D1-like receptors agonist SKF38393 to the bilateral dorsal hippocampus largely prevented OTT, as demonstrated by the ability of the diazepam treatment to produce significant anxiolytic-like effects in trial 2 after a one-day interval. These findings suggest that OTT to the EPM test may occur via the activation of NMDA receptors and the inactivation of D1-like receptors in certain brain regions, including the hippocampus.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China.
authors.forename: Cheng-Long
authors.initials: CL
authors.lastname: Yu
authors.affiliation: Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China.
authors.forename: Yue-Xiong
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
authors.affiliation: Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China. Electronic address: qixin_zhou@126.com.
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Laboratory of Learning and Memory, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS, Kunming 650223, China; CAS Center for Excellence in Brain Science, 320 Yue Yang Road, Shanghai 200031, China. Electronic address: lxu@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016291:Dizocilpine Maleate; D003975:Diazepam
keywords: Anxiety; Dopaminergic system; Elevated plus maze; Glutamatergic system; One-trial tolerance