The effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin on the anxiolytic effect of citalopram in conditioned fear stress in the rat.
Several studies have shown that the α₁-adrenoreceptor is involved in controlling extracellular serotonin levels. The administration of the α₁-adrenoreceptor antagonist prazosin was shown to decrease extracellular serotonin levels in the hippocampus, the prefrontal cortex and the raphe nucleus, while the administration of the α₁-adrenoreceptor agonist cirazoline was shown to increase serotonin levels. Furthermore, the elevation of serotonin levels induced by the selective serotonin reuptake inhibitor (SSRI) citalopram was attenuated by prazosin. Thus, α₁-adrenoreceptor antagonists may affect SSRI-induced increases in extracellular serotonin levels and their antidepressive and anxiolytic effects. However, little is known about the influence of α₁-adrenoreceptor antagonists on the behavioral pharmacological effects of SSRIs. The conditioned fear stress-induced freezing behavior is an animal model of anxiety and can detect the anxiolytic effect of SSRIs. To clarify whether an α₁-adrenoreceptor antagonist affects the anxiolytic action of SSRIs, we examined the effects of the co-administration of the α₁-adrenoreceptor antagonist prazosin and the SSRI citalopram using the contextual conditioned fear stress model. Low-dose prazosin (0.03 mg/kg) significantly attenuated the citalopram (3 mg/kg)-induced decrease in conditioned freezing. Moreover, high-dose (0.5 mg/kg), but not low-dose (0.03 mg/kg), prazosin significantly attenuated citalopram (10 mg/kg)-induced decreases in conditioned freezing. These drugs did not affect the spontaneous motor activity of the rats. Therefore, these results suggest that blocking the α₁-adrenoreceptor decreases the anxiolytic effect of citalopram.
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Naoki
N
Takamura
Takahiro
T
Masuda
Takeshi
T
Inoue
Shin
S
Nakagawa
Tsukasa
T
Koyama
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015283:Citalopram / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005239:Fear / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000523:psychology
D058668:Adrenergic alpha-1 Receptor Antagonists; D014151:Anti-Anxiety Agents; D015283:Citalopram; D011224:Prazosin; D017367:Selective Serotonin Reuptake Inhibitors