5-HT1A-Receptor Subtype Mediates the Effect of Fluvoxamine, a Selective Serotonin Reuptake Inhibitor, on Marble-Burying Behavior in Mice

Abstract

The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in a model of anxiety and/or obsessive compulsive disorder (OCD) in mice. In the anxiety/OCD model, marble-burying behavior, marble-burying was significantly suppressed by fluvoxamine at 30 and 60 mg/kg, p.o. and the monoamine reuptake inhibitor clomipramine, at 60 mg/kg, p.o. No suppressive effect, however, was observed by the selective norepinephrine reuptake inhibitor desipramine at doses from 15 to 60 mg/kg, p.o. Suppressive effects were obtained by the serotonergic anxiolytic buspirone at 30 and 60 mg/kg, p.o. and the benzodiazepine anxiolytic diazepam at 10 mg/kg, p.o. The effect of fluvoxamine on marble-burying was slightly attenuated after repeated administration. On the other hand, both the effects of buspirone and diazepam completely disappeared after repeated administration. Effect of fluvoxamine on the marble-burying was unaffected by the 5-HT2 antagonist ritanserin. However, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) inhibited the suppressive effect of fluvoxamine on the marble-burying. From these results, the 5-HT1A-receptor subtype may be involved in the suppressive effect of fluvoxamine on the marble-burying, but the 5-HT2-receptor subtype is not involved in this effect.