title: Opposite effects of nefazodone in two human models of anxiety.
abstract: 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.
authors.affiliation: Department of Neurology, Psychiatry and Medical Psychology, FFMRP, University of São Paulo, Av. Nove de Julho, 980, 14025-000 Ribeirão Preto, SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Silva
authors.forename: L A
authors.initials: LA
authors.lastname: Hetem
authors.forename: F S
authors.initials: FS
authors.lastname: Guimarães
authors.forename: F G
authors.initials: FG
authors.lastname: Graeff
mesh_terms: 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*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; C051752:nefazodone