Effects of the co-administration of 5-HT1A receptor antagonists with an SSRI in conditioned fear stress-induced freezing behavior.
The effects of the co-administration of the serotonin (5-HT) 1A receptor antagonists NAN-190 or (+)-WAY100135 with a selective 5-HT reuptake inhibitor (SSRI) citalopram on conditioned fear stress (CFS)-induced freezing behavior, which is the animal model of anxiety, were examined. The inhibitory effects of co-administration of NAN-190 (0.1-10 mg/kg) with citalopram on CFS-induced freezing were potent; in particular, at 0.1 and 0.25 mg/kg, NAN-190 significantly enhanced the effect of citalopram alone. At 0.1 mg/kg, (+)-WAY100135 also markedly enhanced the inhibitory effect of citalopram on freezing behavior. These findings suggest that 5-HT1A receptor antagonist, particularly at low doses, enhances the antifreezing effect of citalopram by blocking the autoreceptor-mediated negative feedback mechanisms of the 5-HT neuron. These experimental results concur with clinical findings that 5-HT1A receptor antagonist pindolol potentiates the effect of 5-HT reuptake inhibitors.
Hashimoto
S
S
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
Inoue
T
T
Koyama
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015283:Citalopram / Q000008:administration & dosage; D003213:Conditioning, Psychological / Q000187:drug effects; D004357:Drug Synergism; D005239:Fear / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D013312:Stress, Physiological / Q000503:physiopathology
D015283:Citalopram; D010879:Piperazines; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C081293:WAY 100135