Opposite effects of nefazodone in two human models of anxiety.
OBJECTIVE
To explore further the role of serotonin (5-HT) in anxiety, the effects of the 5-HT reuptake inhibitor and 5-HT2A receptor antagonist nefazodone (NF) were measured in two human models of anxiety.


METHODS
Twenty-nine adult healthy volunteers of both sexes underwent conditioning of skin conductance responses (CSCR) to a tone associated to an aversive white noise. Another 34 subjects performed a simulated public speaking (SPS) task, seemingly related to unconditioned fear. In both tests, subjective states were evaluated through the visual analogue mood scale (VAMS) and a bodily symptoms scale (BSS). In each experiment, subjects were randomly divided into three groups, which received 100 mg NF, 200 mg NF or placebo under double-blind condition.


RESULTS
In the CSCR test, NF decreased the number of spontaneous fluctuations of skin conductance (F=4.94; df=2,26; P=0.015). In addition, the increase in VAMS anxiety factor induced by the conditioning task was attenuated by NF (F=11.11; df=2,26; P<0.001). In contrast, the rise of VAMS anxiety induced by SPS was enhanced by NF (F=8.01; df=2,31; P=0.002).


CONCLUSIONS
These results indicate that NF decreases conditioned anxiety, while enhancing unconditioned fear. Since the effects of NF may be due to impairment of 5-HT neurotransmission, consequent to overstimulation of autosomic 5-HT1A receptors and blockade of post-synaptic 5-HT2A receptors, the present results support the hypothesis that 5-HT facilitates conditioned anxiety, which may be related to generalised anxiety disorder, while inhibiting unconditioned fear, supposedly related to panic disorder.
Silva
M
M
Department of Neurology, Psychiatry and Medical Psychology, FFMRP, University of São Paulo, Av. Nove de Julho, 980, 14025-000 Ribeirão Preto, SP, Brazil.
Hetem
L A
LA
Guimarães
F S
FS
Graeff
F G
FG
D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013060:Speech / Q000187:drug effects* / Q000502:physiology; D018709:Statistics, Nonparametric; D014230:Triazoles / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C051752:nefazodone