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Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat.
Eur J Pharmacol. 2008 May 31; 586(1-3):171-8.EJ

Abstract

This study investigated the effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT(1B/1D) receptor antagonist GR 127,935 with a subactive dose of citalopram [selective serotonin (5-HT) reuptake inhibitor (SSRI)] on the expression of conditioned freezing, an index of fear. In the present study, acute administration of citalopram (s.c.) reduced freezing significantly at high doses (10, 30 and 100 mg/kg), while showing no significant effect at low doses (1 and 3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg) reduced freezing markedly and significantly, as compared with either drug alone. However, the addition of GR 127,935 (4 mg/kg) did not potentiate the effects of citalopram (3 mg/kg) on freezing and did not enhance the effect of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) or GR 127,935 (4 mg/kg) gave no effect on high-dose citalopram (30 mg/kg)-induced inhibition of freezing behavior. These results suggest that co-administration of WAY 100,635 (0.15 mg/kg) strengthens the anxiolytic effect of citalopram (3 mg/kg) by facilitating central 5-HT neurotransmission. Since GR 127,935 (4 mg/kg) failed to accelerate the inhibition of freezing induced by citalopram (3 mg/kg) with WAY 100,635 (0.15 mg/kg) or citalopram (3 mg/kg) alone, it is suggested that blocking 5-HT1A receptors is more effective in facilitating the anxiolytic effect of citalopram than blocking 5-HT1B/1D receptors.

Authors+Show Affiliations

Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18423441

Citation

Muraki, Ihoko, et al. "Effect of Co-administration of the Selective 5-HT1A Receptor Antagonist WAY 100,635 and Selective 5-HT1B/1D Receptor Antagonist GR 127,935 On Anxiolytic Effect of Citalopram in Conditioned Fear Stress in the Rat." European Journal of Pharmacology, vol. 586, no. 1-3, 2008, pp. 171-8.
Muraki I, Inoue T, Koyama T. Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat. Eur J Pharmacol. 2008;586(1-3):171-8.
Muraki, I., Inoue, T., & Koyama, T. (2008). Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat. European Journal of Pharmacology, 586(1-3), 171-8. https://doi.org/10.1016/j.ejphar.2008.01.040
Muraki I, Inoue T, Koyama T. Effect of Co-administration of the Selective 5-HT1A Receptor Antagonist WAY 100,635 and Selective 5-HT1B/1D Receptor Antagonist GR 127,935 On Anxiolytic Effect of Citalopram in Conditioned Fear Stress in the Rat. Eur J Pharmacol. 2008 May 31;586(1-3):171-8. PubMed PMID: 18423441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/1D receptor antagonist GR 127,935 on anxiolytic effect of citalopram in conditioned fear stress in the rat. AU - Muraki,Ihoko, AU - Inoue,Takeshi, AU - Koyama,Tsukasa, Y1 - 2008/02/05/ PY - 2007/09/15/received PY - 2007/12/10/revised PY - 2008/01/28/accepted PY - 2008/4/22/pubmed PY - 2008/9/3/medline PY - 2008/4/22/entrez SP - 171 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 586 IS - 1-3 N2 - This study investigated the effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT(1B/1D) receptor antagonist GR 127,935 with a subactive dose of citalopram [selective serotonin (5-HT) reuptake inhibitor (SSRI)] on the expression of conditioned freezing, an index of fear. In the present study, acute administration of citalopram (s.c.) reduced freezing significantly at high doses (10, 30 and 100 mg/kg), while showing no significant effect at low doses (1 and 3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg) reduced freezing markedly and significantly, as compared with either drug alone. However, the addition of GR 127,935 (4 mg/kg) did not potentiate the effects of citalopram (3 mg/kg) on freezing and did not enhance the effect of WAY 100,635 (0.15 mg/kg) with citalopram (3 mg/kg). Co-administration of WAY 100,635 (0.15 mg/kg) or GR 127,935 (4 mg/kg) gave no effect on high-dose citalopram (30 mg/kg)-induced inhibition of freezing behavior. These results suggest that co-administration of WAY 100,635 (0.15 mg/kg) strengthens the anxiolytic effect of citalopram (3 mg/kg) by facilitating central 5-HT neurotransmission. Since GR 127,935 (4 mg/kg) failed to accelerate the inhibition of freezing induced by citalopram (3 mg/kg) with WAY 100,635 (0.15 mg/kg) or citalopram (3 mg/kg) alone, it is suggested that blocking 5-HT1A receptors is more effective in facilitating the anxiolytic effect of citalopram than blocking 5-HT1B/1D receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18423441/Effect_of_co_administration_of_the_selective_5_HT1A_receptor_antagonist_WAY_100635_and_selective_5_HT1B/1D_receptor_antagonist_GR_127935_on_anxiolytic_effect_of_citalopram_in_conditioned_fear_stress_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00116-7 DB - PRIME DP - Unbound Medicine ER -