Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine.
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.
Quednow
Boris B
BB
Department of Psychiatry, University of Bonn, Bonn, Germany. boris.quednow@ukb.uni-bonn.de
Wagner
Michael
M
Westheide
Jens
J
Beckmann
Katrin
K
Bliesener
Niclaas
N
Maier
Wolfgang
W
Kühn
Kai-Uwe
KU
D000161:Acoustic Stimulation; D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D005500:Follow-Up Studies; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D000077152:Olanzapine; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors; D012016:Reference Values; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D058830:Serotonin 5-HT2 Receptor Antagonists; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D050637:Receptors, Dopamine D3; D058830:Serotonin 5-HT2 Receptor Antagonists; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D000077152:Olanzapine