Pattern of acute induction of Homer1a gene is preserved after chronic treatment with first- and second-generation antipsychotics: effect of short-term drug discontinuation and comparison with Homer1a-interacting genes.
Homer1a is a glutamate-related gene whose expression is induced by antipsychotics acutely (i.e. 90 min after treatment). Acute Homer1a expression is preserved after prolonged antipsychotic treatments, while the effects of short-term discontinuation after chronic antipsychotic treatment have not yet been assessed. Here, we studied early and long-term effects on gene expression by antipsychotics for Homer1a and other components of glutamatergic synapses. In the first paradigm, we evaluated Homer1a acute expression by single administration of antipsychotics (haloperidol 0.8 mg/kg, ziprasidone 10 and 4 mg/kg, clozapine 15 mg/kg). Haloperidol and ziprasidone induced Homer1a in the striatum. Induction by ziprasidone was dose-dependent. These results suggest that acute Homer1a expression correlates with dopaminergic affinity and motor side effects of antipsychotics. In the second paradigm, we studied antipsychotic-mediated long-term changes in Homer1a and glutamate-related genes. Rats were treated (21 days) with haloperidol 0.8 mg/kg, ziprasidone 4 mg/kg, or vehicle, and then sacrificed at 90 min (early time-point) or 24 h (delayed time-point) after last injection. Gene expression at these two time-points was compared. Homer1a preserved its pattern of expression at the early but not at the delayed time-point. Significant changes were also observed for PSD-95. The results suggest that Homer1a preserves its expression profile after chronic antipsychotics.
Laboratory of Molecular Psychiatry and Psychopharmacotherapy, Section of Psychiatry, Department of Neuroscience, University School of Medicine 'Federico II', Naples, Italy.
Felice
F
Iasevoli
Alberto
A
Ambesi-Impiombato
Germano
G
Fiore
Fabio
F
Panariello
Giovanni
G
Muscettola
Andrea
A
de Bartolomeis
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000633:toxicity; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage* / Q000633:toxicity; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage* / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage* / Q000633:toxicity; D013997:Time Factors; D015854:Up-Regulation
D014150:Antipsychotic Agents; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010879:Piperazines; D012333:RNA, Messenger; D013844:Thiazoles; C092292:ziprasidone; D006220:Haloperidol