Abstract
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.
MeSH terms
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Animals
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Antipsychotic Agents / administration & dosage
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Antipsychotic Agents / classification
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Antipsychotic Agents / pharmacology*
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Benzodiazepines
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Carrier Proteins / biosynthesis*
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Carrier Proteins / genetics
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Carrier Proteins / physiology
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Caudate Nucleus / drug effects
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Caudate Nucleus / metabolism
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Corpus Striatum / drug effects*
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Corpus Striatum / metabolism
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Disks Large Homolog 4 Protein
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Enkephalins / biosynthesis
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Enkephalins / genetics
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Frontal Lobe / drug effects
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Frontal Lobe / metabolism
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Haloperidol / pharmacology*
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Homer Scaffolding Proteins
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology
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Neuronal Plasticity / drug effects
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Neuropeptides / biosynthesis*
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Neuropeptides / genetics
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Neuropeptides / physiology
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Nucleus Accumbens / drug effects
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Nucleus Accumbens / metabolism
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Olanzapine
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Parietal Lobe / drug effects
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Parietal Lobe / metabolism
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Pirenzepine / analogs & derivatives*
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Pirenzepine / pharmacology*
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism
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Putamen / drug effects
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Putamen / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Receptors, Metabotropic Glutamate / physiology
Substances
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Antipsychotic Agents
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Carrier Proteins
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Enkephalins
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Homer Scaffolding Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Neuropeptides
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RNA, Messenger
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Receptors, Metabotropic Glutamate
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postsynaptic density proteins
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Benzodiazepines
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Pirenzepine
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Haloperidol
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Olanzapine