Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 135, Issue -, Pages 40-45Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2015.05.009
Keywords
Anxiety; Elevated plus maze; One-trial tolerance; Glutamatergic system; Dopaminergic system
Funding
- National Basic Research Program of China from the Ministry of Science and Technology of China [2013CB835103]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB02020002]
- National Science Foundation of China [81171294, 31100775, 31371141]
- Science and Technology Program of Yunnan Province [2013GA003]
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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 anxiolylic-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 1.5 h 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. (C) 2015 Elsevier Inc. All rights reserved.
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