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

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 (0.8 mg kg –1 ), risperidone (3 mg kg –1 ), olanzapine (2.5 mg kg –1 ) and (-)-sulpiride (50 mg 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.