Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions

Psychiatry Res. 2010 May 15;177(1-2):255-60. doi: 10.1016/j.psychres.2010.02.009. Epub 2010 Mar 21.

Abstract

Homer1a and Yotiao are two post-synaptic density proteins at the crossroad of dopamine-glutamate neurotransmission. Homer1a has been implicated in the pathophysiology of schizophrenia and is differentially induced by typical and atypical antipsychotics, perhaps according to their dopaminergic profile. Yotiao has been involved in glutamate and dopamine post-synaptic signalling. Here, we seek to determine whether Homer1a and Yotiao might be implicated in post-synaptic response to antipsychotics with affinity to different dopamine D(2) receptors: haloperidol (0.8mg kg(-1)), risperidone (3mg kg(-1)), olanzapine (2.5mg kg(-1)) and (-)-sulpiride (50mg kg(-1)). Homer1a expression was significantly induced by haloperidol compared to vehicle and to atypical antipsychotics in almost all striatal sub-regions. Atypical antipsychotics induced the gene in the lateral putamen and in the core of the accumbens only. All antipsychotics, with the exclusion of sulpiride, elicited a dorsolateral-to-ventromedial distribution pattern of Homer1a expression. No significant induction was detected for Yotiao. These results suggest that the quantitative and topographical pattern of Homer1a expression may putatively be related to antipsychotics affinity and/or occupancy at dopamine D(2) receptors.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Benzodiazepines / pharmacology
  • Brain Mapping
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Corpus Striatum / anatomy & histology*
  • Corpus Striatum / drug effects*
  • Gene Expression Regulation / drug effects*
  • Haloperidol / pharmacology
  • Homer Scaffolding Proteins
  • Male
  • Olanzapine
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Risperidone / pharmacology
  • Sulpiride / pharmacology

Substances

  • Antipsychotic Agents
  • Carrier Proteins
  • Homer Scaffolding Proteins
  • RNA, Messenger
  • Benzodiazepines
  • Sulpiride
  • Haloperidol
  • Risperidone
  • Olanzapine