Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine

Psychopharmacology (Berl). 2008 Mar;196(4):673-84. doi: 10.1007/s00213-007-1016-4. Epub 2007 Dec 21.


Rationale: High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor.

Objectives: We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation.

Materials and methods: Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence.

Results: During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms.

Conclusions: Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.

Publication types

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

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use*
  • Dopamine D2 Receptor Antagonists
  • Female
  • Flupenthixol / adverse effects
  • Flupenthixol / therapeutic use
  • Fluphenazine / adverse effects
  • Fluphenazine / therapeutic use
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Motivation*
  • Neostriatum / drug effects
  • Nucleus Accumbens / drug effects
  • Olanzapine
  • Oxygen / blood
  • Psychomotor Performance / drug effects
  • Reaction Time / drug effects
  • Receptors, Dopamine D2 / drug effects
  • Reward*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology


  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D2
  • Benzodiazepines
  • Flupenthixol
  • Haloperidol
  • Olanzapine
  • Fluphenazine
  • Oxygen