期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 586, 期 1-3, 页码 171-178出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.01.040
关键词
SSRI [selective serotonin (5-HT) reuptake inhibitor]; selective 5-HT1A receptor antagonist; selective 5-HT1B/1D receptor antagonist; anxiety; conditioned fear stress
This study investigated the effect of co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 and selective 5-HT1B/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. (C) 2008 Elsevier B.V. All rights reserved.
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