Effect of chronic administration of flesinoxan and fluvoxamine on freezing behavior induced by conditioned fear.
The present study investigated the acute effects of flesinoxan (a selective 5-HT(1A) receptor agonist), fluvoxamine (a selective serotonin reuptake inhibitor) and their co-administration on the expression of conditioned freezing, and index of anxiety in rats. This study also examined the acute effects of fluvoxamine and flesinoxan following chronic flesinoxan or chronic fluvoxamine on the expression of conditioned freezing. Acute administration of flesinoxan (s.c.; 0.1-3 mg/kg) reduced freezing dose dependently, and fluvoxamine (i.p.) at a high dose (60 mg/kg) reduced freezing significantly. Acute co-administration of fluvoxamine (30 mg/kg) and flesinoxan (0.3 mg/kg) showed an additive inhibitory effect on freezing. Chronic flesinoxan treatment (0.3 mg/kg, for 13 days) did not affect the inhibitory effect of acute flesinoxan treatment, but enhanced that of acute fluvoxamine (30 mg/kg) on conditioned freezing. Chronic fluvoxamine treatment (30 mg/kg, for 13 days) enhanced the inhibitory effect of acute fluvoxamine (30 mg/kg) and the inhibitory effect of acute flesinoxan (0.3 mg/kg) on conditioned freezing. These results suggest that co-administration of a selective serotonin reuptake inhibitor and a 5-HT(1A) receptor agonist is useful for the treatment of anxiety disorders.
Li
X B
XB
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan. xiao@med.hokudai.ac.jp
Inoue
T
T
Hashimoto
S
S
Koyama
T
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000523:psychology*; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D016666:Fluvoxamine; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C056895:flesinoxan