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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.
Methods Find Exp Clin Pharmacol 2005; 27(4):245-55MF

Abstract

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.

Authors+Show Affiliations

Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Spring House, Pennsylvania 19477-0776, USA. avaidya@prdus.jnj.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16082425

Citation

Vaidya, A H., et al. "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." Methods and Findings in Experimental and Clinical Pharmacology, vol. 27, no. 4, 2005, pp. 245-55.
Vaidya AH, Rosenthal DI, Lang W, et al. 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. Methods Find Exp Clin Pharmacol. 2005;27(4):245-55.
Vaidya, A. H., Rosenthal, D. I., Lang, W., Crooke, J. J., Benjamin, D., Ilyin, S. E., & Reitz, A. B. (2005). 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. Methods and Findings in Experimental and Clinical Pharmacology, 27(4), pp. 245-55.
Vaidya AH, et al. 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. Methods Find Exp Clin Pharmacol. 2005;27(4):245-55. PubMed PMID: 16082425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Vaidya,A H, AU - Rosenthal,D I, AU - Lang,W, AU - Crooke,J J, AU - Benjamin,D, AU - Ilyin,S E, AU - Reitz,A B, PY - 2005/8/6/pubmed PY - 2005/9/2/medline PY - 2005/8/6/entrez SP - 245 EP - 55 JF - Methods and findings in experimental and clinical pharmacology JO - Methods Find Exp Clin Pharmacol VL - 27 IS - 4 N2 - 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. SN - 0379-0355 UR - https://www.unboundmedicine.com/medline/citation/16082425/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_ L2 - http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=893584 DB - PRIME DP - Unbound Medicine ER -