Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine

Biol Psychiatry. 2006 Mar 15;59(6):536-45. doi: 10.1016/j.biopsych.2005.07.012. Epub 2005 Sep 1.


Background: Schizophrenic patients exhibit impairments in prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR). Recent studies suggested that PPI deficits and habituation deficits are normalized after antipsychotic treatment. Despite clear evidence of gating and habituation mechanisms in animal models, it is still unknown which neurotransmitter systems are involved in schizophrenic patients. Thus, we compared the effects of a combined 5-HT2A/D2 and a pure D2/D3 antagonist on PPI and habituation of ASR in patients with schizophrenia.

Methods: The ASR was measured in 37 acute schizophrenic patients who were randomized and double-blinded as to treatment with amisulpride or olanzapine. Patients were assessed during the first week and after four and eight weeks of treatment. Twenty healthy matched control subjects were examined likewise.

Results: Schizophrenic patients showed a significant PPI deficit and significantly decreased startle amplitude at baseline. The gating deficit disappeared after antipsychotic treatment in both treatment groups. Amisulpride sensitized the startle amplitude, whereas startle amplitude was not changed by olanzapine. After correcting for startle amplitude, patients did not show a habituation deficit; however, amisulpride accelerated habituation, whereas olanzapine had no effect.

Conclusions: Our findings suggest that the PPI-restoring effect of antipsychotics is probably attributed to a dopamine D2 receptor blockade.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Adult
  • Amisulpride
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use*
  • Attention / drug effects*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Dopamine D2 Receptor Antagonists
  • Follow-Up Studies
  • Habituation, Psychophysiologic / drug effects*
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Olanzapine
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Reference Values
  • Reflex, Startle / drug effects*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Serotonin 5-HT2 Receptor Antagonists
  • Sulpiride / adverse effects
  • Sulpiride / analogs & derivatives*
  • Sulpiride / therapeutic use


  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D3
  • Serotonin 5-HT2 Receptor Antagonists
  • Benzodiazepines
  • Sulpiride
  • Amisulpride
  • Olanzapine