Oral buspirone causes a shift in the dose-response curve between the elevated-plus maze and Vogel conflict tests in Long-Evans rats: relation of brain levels of buspirone and 1-PP to anxiolytic action

• Published in: Methods and findings in experimental and clinical pharmacology Vol. 27; no. 4; p. 245
• Main Authors: Vaidya, A H, Rosenthal, D I, Lang, W, Crooke, J J, Benjamin, D, Ilyin, S E, Reitz, A B
• Format: Journal Article
• Language: English
• Published: Spain 01.05.2005
• Subjects: Administration, Oral; Animals; Anti-Anxiety Agents - blood; Anti-Anxiety Agents - pharmacokinetics; Anti-Anxiety Agents - pharmacology; Behavior, Animal - drug effects; Brain - metabolism; Brain Chemistry; Buspirone - analogs & derivatives; Buspirone - blood; Buspirone - metabolism; Buspirone - pharmacokinetics; Buspirone - pharmacology; Conflict (Psychology); Dose-Response Relationship, Drug; Male; Maze Learning - drug effects; Motor Activity - drug effects; Rats; Rats, Long-Evans; Serotonin Receptor Agonists - blood; Serotonin Receptor Agonists - pharmacokinetics; Serotonin Receptor Agonists - pharmacology
• ISSN: 0379-0355
• DOI: 10.1358/mf.2005.27.4.893584

Most studies concerning the effects of oral buspirone in the rat elevated plus-maze (EPM) test, spontaneous motor activity (SMA) test, and Vogel conflict (VC) test have used Sprague-Dawley or Wistar rats. Although it has been documented that the behavior of Long-Evans rats is more sensitive to detection of anxiolytics when compared to the aforementioned strains, the effects of oral buspirone have not been fully characterized in the Long-Evans strain in the EPM and VC tests. Thus, we studied the effects of orally administered buspirone (0.03-10.0 mg/kg) in the EPM, SMA, and VC (0.3-60.0 mg/kg) tests in Long-Evans rats. In a separate experiment, brain and plasma concentrations of buspirone and 1-(2-pyrimidinyl)-piperazine (1-PP) were determined after oral administration of buspirone (0.3 and 10 mg/kg) to relate the behavioral effects of buspirone with brain and plasma concentrations of buspirone and 1-PP. Our results showed that buspirone exhibited an inverted-U-shaped dose-response curve in both the EPM and the VC tests. In the EPM, buspirone produced anxiolytic activity in a low, narrow dose-range (0.03, 0.1, 0.3 mg/kg, p.o.) with maximum efficacy at 0.3 mg/kg, whereas in the VC test, significant anxiolytic activity was observed in a high, narrow dose-range (10, 30 mg/kg, p.o.) with maximum efficacy occurring at 10 mg/kg. In the SMA test, buspirone (10 mg/kg, p.o.) significantly decreased horizontal activity and vertical movements suggestive of sedation. Also, one hour following oral doses of buspirone (0.3 and 10 mg/kg), both buspirone and 1-PP concentrations were higher in brain when compared with those in plasma. Additionally, the concentrations of 1-PP were always higher in brain and in plasma compared with the concentrations of buspirone. Of particular interest is our finding of the shift in the dose-response curve between the EPM and VC tests. This shift in the dose-response curve is discussed in relation to brain levels of buspirone and 1-PP levels and their anxiolytic action.