Abstract
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test, where BW 723C86 (0.5-50 mg kg-1, s.c. 30 min pretest) modestly, but significantly increased punished, but not unpublished responding. 4.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-Siefter 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, but 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.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adham N., Kao H. T., Schecter L. E., Bard J., Olsen M., Urquhart D., Durkin M., Hartig P. R., Weinshank R. L., Branchek T. A. Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408–412. doi: 10.1073/pnas.90.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baxter G., Kennett G., Blaney F., Blackburn T. 5-HT2 receptor subtypes: a family re-united? Trends Pharmacol Sci. 1995 Mar;16(3):105–110. doi: 10.1016/s0165-6147(00)88991-9. [DOI] [PubMed] [Google Scholar]
- Blackburn T. P., Baxter G. S., Kennett G. A., King F. D., Piper D. C., Sanger G. J., Thomas D. R., Upton N., Wood M. D. BRL 46470A: a highly potent, selective and long acting 5-HT3 receptor antagonist with anxiolytic-like properties. Psychopharmacology (Berl) 1993;110(3):257–264. doi: 10.1007/BF02251279. [DOI] [PubMed] [Google Scholar]
- Clineschmidt B. V., Reiss D. R., Pettibone D. J., Robinson J. L. Characterization of 5-hydroxytryptamine receptors in rat stomach fundus. J Pharmacol Exp Ther. 1985 Dec;235(3):696–708. [PubMed] [Google Scholar]
- Dawson G. R., Crawford S. P., Collinson N., Iversen S. D., Tricklebank M. D. Evidence that the anxiolytic-like effects of chlordiazepoxide on the elevated plus maze are confounded by increases in locomotor activity. Psychopharmacology (Berl) 1995 Apr;118(3):316–323. doi: 10.1007/BF02245961. [DOI] [PubMed] [Google Scholar]
- File S. E., Hyde J. R. Can social interaction be used to measure anxiety? Br J Pharmacol. 1978 Jan;62(1):19–24. doi: 10.1111/j.1476-5381.1978.tb07001.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foguet M., Hoyer D., Pardo L. A., Parekh A., Kluxen F. W., Kalkman H. O., Stühmer W., Lübbert H. Cloning and functional characterization of the rat stomach fundus serotonin receptor. EMBO J. 1992 Sep;11(9):3481–3487. doi: 10.1002/j.1460-2075.1992.tb05427.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forbes I. T., Kennett G. A., Gadre A., Ham P., Hayward C. J., Martin R. T., Thompson M., Wood M. D., Baxter G. S., Glen A. N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea hydrochloride: the first selective 5-HT1C receptor antagonist. J Med Chem. 1993 Apr 16;36(8):1104–1107. doi: 10.1021/jm00060a019. [DOI] [PubMed] [Google Scholar]
- GELLER I., KULAK J. T., Jr, SEIFTER J. The effects of chlordiazepoxide and chlorpromazine on a punishment discrimination. Psychopharmacologia. 1962 Oct 31;3:374–385. doi: 10.1007/BF00408322. [DOI] [PubMed] [Google Scholar]
- Gibson E. L., Barnfield A. M., Curzon G. Evidence that mCPP-induced anxiety in the plus-maze is mediated by postsynaptic 5-HT2C receptors but not by sympathomimetic effects. Neuropharmacology. 1994 Mar-Apr;33(3-4):457–465. doi: 10.1016/0028-3908(94)90076-0. [DOI] [PubMed] [Google Scholar]
- Handley S. L., Mithani S. Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration model of 'fear'-motivated behaviour. Naunyn Schmiedebergs Arch Pharmacol. 1984 Aug;327(1):1–5. doi: 10.1007/BF00504983. [DOI] [PubMed] [Google Scholar]
- Higgins G. A., Jones B. J., Oakley N. R., Tyers M. B. Evidence that the amygdala is involved in the disinhibitory effects of 5-HT3 receptor antagonists. Psychopharmacology (Berl) 1991;104(4):545–551. doi: 10.1007/BF02245664. [DOI] [PubMed] [Google Scholar]
- Hoyer D., Clarke D. E., Fozard J. R., Hartig P. R., Martin G. R., Mylecharane E. J., Saxena P. R., Humphrey P. P. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev. 1994 Jun;46(2):157–203. [PubMed] [Google Scholar]
- Jones B. J., Costall B., Domeney A. M., Kelly M. E., Naylor R. J., Oakley N. R., Tyers M. B. The potential anxiolytic activity of GR38032F, a 5-HT3-receptor antagonist. Br J Pharmacol. 1988 Apr;93(4):985–993. doi: 10.1111/j.1476-5381.1988.tb11489.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kennett G. A., Bailey F., Piper D. C., Blackburn T. P. Effect of SB 200646A, a 5-HT2C/5-HT2B receptor antagonist, in two conflict models of anxiety. Psychopharmacology (Berl) 1995 Mar;118(2):178–182. doi: 10.1007/BF02245837. [DOI] [PubMed] [Google Scholar]
- Kennett G. A., Whitton P., Shah K., Curzon G. Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists. Eur J Pharmacol. 1989 May 30;164(3):445–454. doi: 10.1016/0014-2999(89)90252-5. [DOI] [PubMed] [Google Scholar]
- Kennett G. A., Wood M. D., Glen A., Grewal S., Forbes I., Gadre A., Blackburn T. P. In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist. Br J Pharmacol. 1994 Mar;111(3):797–802. doi: 10.1111/j.1476-5381.1994.tb14808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kursar J. D., Nelson D. L., Wainscott D. B., Cohen M. L., Baez M. Molecular cloning, functional expression, and pharmacological characterization of a novel serotonin receptor (5-hydroxytryptamine2F) from rat stomach fundus. Mol Pharmacol. 1992 Oct;42(4):549–557. [PubMed] [Google Scholar]
- Loric S., Launay J. M., Colas J. F., Maroteaux L. New mouse 5-HT2-like receptor. Expression in brain, heart and intestine. FEBS Lett. 1992 Nov 9;312(2-3):203–207. doi: 10.1016/0014-5793(92)80936-b. [DOI] [PubMed] [Google Scholar]
- Pellow S., Chopin P., File S. E., Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985 Aug;14(3):149–167. doi: 10.1016/0165-0270(85)90031-7. [DOI] [PubMed] [Google Scholar]
- Pompeiano M., Palacios J. M., Mengod G. Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res Mol Brain Res. 1994 Apr;23(1-2):163–178. doi: 10.1016/0169-328x(94)90223-2. [DOI] [PubMed] [Google Scholar]
- Schmuck K., Ullmer C., Engels P., Lübbert H. Cloning and functional characterization of the human 5-HT2B serotonin receptor. FEBS Lett. 1994 Mar 28;342(1):85–90. doi: 10.1016/0014-5793(94)80590-3. [DOI] [PubMed] [Google Scholar]
- To Z. P., Bonhaus D. W., Eglen R. M., Jakeman L. B. Characterization and distribution of putative 5-ht7 receptors in guinea-pig brain. Br J Pharmacol. 1995 May;115(1):107–116. doi: 10.1111/j.1476-5381.1995.tb16327.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Tol H. H., Bunzow J. R., Guan H. C., Sunahara R. K., Seeman P., Niznik H. B., Civelli O. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991 Apr 18;350(6319):610–614. doi: 10.1038/350610a0. [DOI] [PubMed] [Google Scholar]
- Villarroya M., Gandía L., Lara B., Albillos A., López M. G., García A. G. Dotarizine versus flunarizine as calcium antagonists in chromaffin cells. Br J Pharmacol. 1995 Jan;114(2):369–376. doi: 10.1111/j.1476-5381.1995.tb13236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitton P., Curzon G. Anxiogenic-like effect of infusing 1-(3-chlorophenyl) piperazine (mCPP) into the hippocampus. Psychopharmacology (Berl) 1990;100(1):138–140. doi: 10.1007/BF02245806. [DOI] [PubMed] [Google Scholar]
- Yadin E., Thomas E., Grishkat H. L., Strickland C. E. The role of the lateral septum in anxiolysis. Physiol Behav. 1993 Jun;53(6):1077–1083. doi: 10.1016/0031-9384(93)90362-j. [DOI] [PubMed] [Google Scholar]
