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 …

I Muraki, T Inoue, T Koyama - European journal of pharmacology, 2008 - Elsevier
I Muraki, T Inoue, T Koyama
European journal of pharmacology, 2008Elsevier
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 (sc) 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 …
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.
Elsevier
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