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Abstract
Our previous study showed that conditioned fear stress (CFS) increased serotonin (5-HT)
metabolism in the medial prefrontal cortex and induced freezing behavior. Although
these results could support the 5-HT hypothesis of anxiety, the functional significance
of the 5-HT response to stress is unclear. In this study, the effects of 5-HT reuptake
inhibitors, agonists, antagonists, and diazepam on freezing behavior induced by CFS
were examined using a time-sampling procedure. Various doses of test compounds were
administered subcutaneously to rats 24 h after the last session of repeated foot-shock
for 5 days. Rats were again placed in the shock chamber without shocks 20 min after
injections of drugs, and observed. Diazepam (1 mg/kg) and the 5-HT1A agonist ipsapirone
(0.5-10 mg/kg) significantly inhibited freezing behavior. L-5-Hydroxytryptophan (with
benserazide) and the selective 5-HT reuptake inhibitor citalopram (10 mg/kg) reduced
freezing behavior. The 5-HT2 antagonists ICI169,369 and ketanserin failed to change
freezing behavior. p-Chlorophenylalanine (200 mg/kg) administered 15 h before the
test did not affect freezing. The effect of ipsapirone was not modified in rats with
lesions of 5-HT neurons, produced by p-chloroamphetamine (2 x 10 mg/kg). In conclusion,
these results suggest the anxiolytic potential of ipsapirone and citalopram, and support
the hypothesis that the facilitation of 5-HT neurotransmission decreases anxiety.