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.