Effects of the 5-HT2B receptor agonist, BW 723C86, on three rat models of anxiety

被引:82
作者
Kennett, GA [1 ]
Bright, F [1 ]
Trail, B [1 ]
Baxter, GS [1 ]
Blackburn, TP [1 ]
机构
[1] SMITHKLINE BEECHAM PHARMACEUT, NEUROL RES DEPT, HARLOW CM19 5AW, ESSEX, ENGLAND
关键词
5-HT2B receptor; 5-HT2C receptor; anxiety; BW; 723C86;
D O I
10.1111/j.1476-5381.1996.tb15304.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 BW 723C86 (3 and 10 mg kg(-1), s.c. 30 min pretest), a 5-HT2B receptor agonist, increased total interaction, but not locomotion in a rat social interaction test, a profile consistent with anxiolysis. 2 The effect of BW 723C86 in the social interaction test is likely to be 5-HT2B, receptor-mediated as it was prevented by pretreatment with the 5-HT2C/2B receptor antagonist, SB 200646A. (1 and 2 mg kg(-1) p.o., 1 h pretest) which did not affect basal levels of social interaction at the doses used. 3 An anxiolytic-like action was also observed in the rat Geller-Seifter conflict test, where BW 723C86 (0.5-50 mg kg(-1), s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4 In a rat 5 min elevated x-maze test. BW 723C86 (1-10 mg kg(-1), s.c.) had no significant effect. 5 The maximal anxiolytic-like effect of BW 723C86 approached that of the benzodiazepine anxiolytic, chloradiazepoxide (5 mg kg(-1), s.c. 30 min pretest) in the social interaction test, but was markedly less in the Geller-Seifter test. The effect of BW 723C86 was also clearly less than chlordiazepoxide in the elevated x-maze procedure where it had no significant effect. 6 In conclusion, BW 723C86 exerted an appreciable anxiolytic-like profile in a rat social interaction test, bur had a weaker effect in the Geller-Siefter and was ineffective in the elevated x-maze test used. These effects are likely to be 5-HT2B receptor-mediated.
引用
收藏
页码:1443 / 1448
页数:6
相关论文
共 37 条
  • [1] CLONING OF ANOTHER HUMAN SEROTONIN RECEPTOR (5-HT1F) - A 5TH 5-HT1 RECEPTOR SUBTYPE COUPLED TO THE INHIBITION OF ADENYLATE-CYCLASE
    ADHAM, N
    KAO, HT
    SCHECHTER, LE
    BARD, J
    OLSEN, M
    URQUHART, D
    DURKIN, M
    HARTIG, PR
    WEINSHANK, RL
    BRANCHEK, TA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) : 408 - 412
  • [2] 5-HT2 RECEPTOR SUBTYPES - A FAMILY RE-UNITED
    BAXTER, G
    KENNETT, G
    BLANEY, F
    BLACKBURN, T
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1995, 16 (03) : 105 - 110
  • [3] BAXTER GS, 1995, IN PRESS BEHAV BRAIN
  • [4] BELL J, 1994, ACNP M
  • [5] BILL DJ, 1995, BRIT J PHARMACOL, V116, pP217
  • [6] BRL-46470A - A HIGHLY POTENT, SELECTIVE AND LONG-ACTING 5-HT(3) RECEPTOR ANTAGONIST WITH ANXIOLYTIC-LIKE PROPERTIES
    BLACKBURN, TP
    BAXTER, GS
    KENNETT, GA
    KING, FD
    PIPER, DC
    SANGER, GJ
    THOMAS, DR
    UPTON, N
    WOOD, MD
    [J]. PSYCHOPHARMACOLOGY, 1993, 110 (03) : 257 - 264
  • [7] CLINESCHMIDT BV, 1985, J PHARMACOL EXP THER, V235, P696
  • [8] CRONIN SM, 1992, BRIT J PHARMACOL, V106, pP128
  • [9] EVIDENCE THAT THE ANXIOLYTIC-LIKE EFFECTS OF CHLORDIAZEPOXIDE ON THE ELEVATED PLUS-MAZE ARE CONFOUNDED BY INCREASES IN LOCOMOTOR-ACTIVITY
    DAWSON, GR
    CRAWFORD, SP
    COLLINSON, N
    IVERSEN, SD
    TRICKLEBANK, MD
    [J]. PSYCHOPHARMACOLOGY, 1995, 118 (03) : 316 - 323
  • [10] DUXON MS, 1995, BRIT J PHARMACOL, V115, pP105