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(Reference retrieved automatically from Google Scholar through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Anxiolytic-like effects of NMDA/glycine-B receptor ligands are abolished during the elevated plus-maze trial 2 in rats

Full text
Author(s):
Bertoglio‚ L.J. ; Carobrez‚ A.P.
Total Authors: 2
Document type: Journal article
Source: Psychopharmacology; v. 170, n. 4, p. 335-342, 2003.
Abstract

Rationale. Drugs enhancing the GABA(A) and/or reducing the NMDA/glycine-B receptor activity produce an anxiolytic effect. Regarding the former drugs (e.g. benzodiazepines), prior elevated plus-maze (EPM) test experience abolishes the trial 2 anxiolytic activity, a phenomenon referred to as 'one-trial tolerance' (OTT). Objectives. The present study examined whether the OTT phenomenon occurs with drugs that reduce the NMDA/glycine-B receptor activity. Methods. Maze-naive and maze-experienced (prior EPM exposure) rats were treated with (+/-)-HA-966 (2.0 or 4.0 mg/kg), (+)-MK-801 (0.03 or 0.06 mg/kg) or memantine (4.0 or 8.0 mg/kg) and submitted to the EPM. To investigate whether the loss of drug responsiveness was due to pharmacological tolerance, rats received memantine (8.0 mg/kg) both 48 h and 30 min before the first EPM exposure. Results. All drugs increased open arms exploration, indicating an anxiolytic effect, in maze-naive but not in maze-experienced rats, in which increased open arms avoidance was observed. An anxiolytic effect was also observed after repeated memantine administration in maze-naive/drug-experienced rats. These effects were observed in the absence of changes in enclosed arms entries, an EPM general exploratory activity index. Conclusions. The present findings extend the OTT phenomenon to drugs that reduce the NMDA/glycine-B-receptor activity, and emphasize the repeated test exposure rather than repeated drug administration as a critical determinant for the drug anxiolytic activity. Considering the mechanisms by which the EPM experience alters the drug effects, the present findings favor the hypothesis in which the OTT phenomenon emerge as a consequence of the development and adoption of an anxiolytic-insensitive behavioral strategy. (AU)

FAPESP's process: 02/13197-2 - Participation of glutamate and nitric oxide on the pathophysiology of neuropsychiatry disorders
Grantee:Francisco Silveira Guimaraes
Support Opportunities: Research Projects - Thematic Grants