Acute administration of antipsychotics modulates Homer striatal gene expression differentially.
Typical and atypical antipsychotics, the mainstay of schizophrenia pharmacotherapy, have been demonstrated to affect differently neuronal gene expression in several preclinical paradigms. Here we report the differential gene expression of the glutamatergic post-synaptic density proteins Homer and PSD-95 in rat forebrain following acute haloperidol or olanzapine treatment. Moreover, considering the extensive interactions between dopaminergic and opioidergic systems we also measured striatal preproenkephalin mRNA. Male Sprague-Dawley rats were treated with haloperidol 1 mg/kg or olanzapine 0.5 mg/kg or vehicle, i.p. and sacrificed 3 h after the injection. Homer gene expression was significantly increased in caudate putamen and nucleus accumbens of rats treated with haloperidol and in the core of accumbens of rats treated with olanzapine. No changes were detected for Homer in prefrontal and parietal cortex in any of the experimental groups. PSD-95 gene expression was not modulated in our paradigm by administration of either typical or atypical antipsychotics. These results (1) suggest a differential modulation of Homer by typical and atypical antipsychotics; (2) confirm that Homer can be induced as an early gene with putative direct effect on neuronal plasticity and (3) demonstrate different response to antipsychotics by different classes of postsynaptic density proteins at glutamatergic synapses.
de Bartolomeis
Andrea
A
Department of Neuroscience and Behavioral Sciences, Section of Psychiatry, University School of Medicine Federico II, Edificio 18, Via Pansini 5, 80131, Naples, Italy. adebart@tiscalinet.it
Aloj
Luigi
L
Ambesi-Impiombato
Alberto
A
Bravi
Daniele
D
Caracò
Corradina
C
Muscettola
Giovanni
G
Barone
Paolo
P
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000145:classification / Q000494:pharmacology*; D001569:Benzodiazepines; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology
D014150:Antipsychotic Agents; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004745:Enkephalins; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C033652:postsynaptic density proteins; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine