EFFECTS OF THE COADMINISTRATION OF 5-HT1A RECEPTOR ANTAGONISTS WITH AN SSRI IN CONDITIONED FEAR STRESS-INDUCED FREEZING BEHAVIOR

HASHIMOTO, S., T. INOUE AND T. KOYAMA. Effects of the co-administratio n of 5-HT1A receptor antagonists with an SSRI in conditioned fear stre ss-induced freezing behavior. PHARMACOL BIOCHEM BEHAV 58(2) 471-475, 1 997.--The effects of the co-administration of the serotonin (5-HT) 1A receptor antagonists NAN-190 or (+)-WAY100135 with a selective 5-HT re uptake inhibitor (SSRI) citalopram on conditioned fear stress (CFS)-in duced freezing behavior, which is the animal model of anxiety, were ex amined. The inhibitory effects of co-administration of NAN 190 (0.1-10 mg/kg) with citalopram on CFS-induced freezing were potent; in partic ular, 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 enhanc ed the inhibitory effect of citalopram on freezing behavior. These fin dings suggest that 5-HT1A receptor antagonist, particularly at low dos es, enhances the antifreezing effect of citalopram by blocking the aut oreceptor-mediated negative feedback mechanisms of the 5-HT neuron. Th ese experimental results concur with clinical findings that 5-HT1A rec eptor antagonist pindolol potentiates the effect of 5-HT reuptake inhi bitors. (C) 1997 Elsevier Science Inc.