Homer 1a Gene Expression Modulation by Antipsychotic Drugs Involvement of the Glutamate Metabotropic System and Effects of D-Cycloserine

Polese, Daniela; Serpis, Antonella Amato de; Ambesi-Impiombato, Alberto; Muscettola, Giovanni; Bartolomeis, Andrea de

doi:10.1016/s0893-133x(02)00371-8

Cited by 61 publications

(56 citation statements)

References 34 publications

(37 reference statements)

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“…Olanzapine in rats increased levels of Homer 1 significantly (Tables 1, 3), a result that was confirmed through QPCR, albeit nonsignificantly (Table 2). Other studies have shown haloperidol increasing Homer in both the caudate putamen and nucleus accumbens of rats (Polese et al, 2002). Clozapine, however, increased Homer in the accumbens only (Polese et al, 2002).…”

Section: Chronic Olanzapine Treatment Sh Fatemi Et Almentioning

confidence: 73%

“…Other studies have shown haloperidol increasing Homer in both the caudate putamen and nucleus accumbens of rats (Polese et al, 2002). Clozapine, however, increased Homer in the accumbens only (Polese et al, 2002). Thus, it appears that haloperidol, clozapine, and olanzapine all increase Homer mRNA levels in various brain sites of rodents modulating glutamate metabotropic system.…”

Section: Chronic Olanzapine Treatment Sh Fatemi Et Almentioning

confidence: 77%

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Chronic Olanzapine Treatment Causes Differential Expression of Genes in Frontal Cortex of Rats as Revealed by DNA Microarray Technique

Fatemi

Reutiman

Folsom

et al. 2006

Neuropsychopharmacol

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Recent emerging biochemical data indicate that several important neuroregulatory genes and proteins may be involved in the etiology of schizophrenia and bipolar disorder. Additionally, the same genes appear to be targets of several psychotropic medications that are used to treat these disorders. Recent DNA microarray studies show that genes involved in synaptic neurotransmission, signal transduction, and glutamate/GABA regulation may be differentially regulated in brains of subjects with schizophrenia. We hypothesized that chronic administration of olanzapine to rats would alter expression of various genes that may be involved in the etiology of schizophrenia and mood disorders. Rats were administered olanzapine (N ¼ 20, 2 mg/kg/day) or sterile saline intraperitoneally (N ¼ 20) daily for 21 days. Control and olanzapine-treated frontal cortices were analyzed using cDNA microarray technology. The results showed significant downregulation of 31 genes and upregulation of 38 genes by greater than two-fold in the drug-treated brains vs controls. Our results provide evidence for altered regulation of genes involved with signal transduction and cell communication, metabolism and energy pathways, transport, immune response, nucleic acid metabolism, and neuronal growth factors. Real-time quantitative RT-PCR analysis verified the direction and magnitude of change in six genes of interest: calbindin 3, homer 1, regulator of G-protein signaling (RGS) 2, pyruvate kinase, Reelin and insulin 2. Western blotting showed significant upregulation in protein products for Reelin 410 and Reelin 180 kDa and downregulation for NMDA3B and RGS2. Our results show for the first time that olanzapine causes changes in levels of several important genes that may be involved in the etiology and treatment of schizophrenia and other psychiatric disorders.

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Section: Chronic Olanzapine Treatment Sh Fatemi Et Almentioning

confidence: 73%

Section: Chronic Olanzapine Treatment Sh Fatemi Et Almentioning

confidence: 77%

Chronic Olanzapine Treatment Causes Differential Expression of Genes in Frontal Cortex of Rats as Revealed by DNA Microarray Technique

Fatemi

Reutiman

Folsom

et al. 2006

Neuropsychopharmacol

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“…Preclinical studies also suggest a dopamine-glutamate interaction based on the converging effect of different drugs, such as amphetamine and PCP on dopamine-modulating factors (dopamine and cAMP-regulated phosphoprotein, DARPP-32) (Svenningsson et al, 2003). Furthermore, antipsychotic compounds are shown to regulate postsynaptic density proteins (e.g., Homer proteins) (Polese et al, 2002), which regulate the function of glutamate receptors.…”

Section: Adx47273 Preclinical Antipsychotic and Procognitive Effects 837mentioning

confidence: 99%

ADX47273 [S-(4-Fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: A Novel Metabotropic Glutamate Receptor 5-Selective Positive Allosteric Modulator with Preclinical Antipsychotic-Like and Procognitive Activities

Liu

Grauer²,

Kelley³

et al. 2008

J Pharmacol Exp Ther

170

178

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Positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) enhance N-methyl-D-aspartate receptor function and may represent a novel approach for the treatment of schizophrenia. ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone], a recently identified potent and selective mGlu5 PAM, increased (9-fold) the response to threshold concentration of glutamate (50 nM) in fluorometric Ca 2ϩ assays (EC 50 ϭ 170 nM) in human embryonic kidney 293 cells expressing rat mGlu5. In the same system, ADX47273 dose-dependently shifted mGlu5 receptor glutamate response curve to the left (9-fold at 1 M) and competed for binding of3 H]quisqualate. In vivo, ADX47273 increased extracellular signal-regulated kinase and cAMP-responsive element-binding protein phosphorylation in hippocampus and prefrontal cortex, both of which are critical for glutamate-mediated signal transduction mechanisms. In models sensitive to antipsychotic drug treatment, ADX47273 reduced rat-conditioned avoidance responding [minimal effective dose (MED) ϭ 30 mg/kg i.p.] and decreased mouse apomorphine-induced climbing (MED ϭ 100 mg/kg i.p.), with little effect on stereotypy or catalepsy. Furthermore, ADX47273 blocked phencyclidine, apomorphine, and amphetamine-induced locomotor activities (MED ϭ 100 mg/kg i.p.) in mice and decreased extracellular levels of dopamine in the nucleus accumbens, but not in the striatum, in rats. In cognition models, ADX47273 increased novel object recognition (MED ϭ 1 mg/kg i.p.) and reduced impulsivity in the fivechoice serial reaction time test (MED ϭ 10 mg/kg i.p.) in rats. Taken together, these effects are consistent with the hypothesis that allosteric potentiation of mGlu5 may provide a novel approach for development of antipsychotic and procognitive agents.The metabotropic glutamate receptor (mGlu) receptor family includes eight G-protein-coupled receptor (GPCR) subtypes classified on the basis of structural homology, Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.108.136580.ABBREVIATIONS: mGlu, metabotropic glutamate receptor; GPCR, G-protein-coupled receptor; PAM, positive allosteric modulator; CPPHA, 2, NMDA, MPEP,

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“…First described for acute cocaine (Brakeman et al, 1997), a growing number of studies demonstrate an enhancement within corticolimbic structures in the expression of mRNA encoding short Homer isoforms by acute exposure to psychoactive drugs Cochran et al, 2002;Fujiyama et al, 2003;Nichols et al, 2003;Nichols and Sanders-Bush, 2002;Polese et al, 2002). Although there is some evidence that the capacity of drugs of abuse to increase short Homer isoform expression is enduring (Ammon et al, 2003;Cochran et al, 2002) or persists throughout repeated drug administration (Ammon et al, 2003;Fujiyama et al, 2003), behavioral sensitization to methamphetamine is not coincident with an altered capacity of this drug to elevate the expression of short Homer isoforms (Fujiyama et al, 2003).…”

Section: Homer Proteins and Behavioral Sensitivity To Drugsmentioning

confidence: 99%

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

Szumlinski

Abernathy

Oleson

et al. 2005

Neuropsychopharmacol

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Homer proteins modulate neuroplasticity in excitatory synapses and are dynamically regulated by cocaine. Whereas acute cocaine elevates immediate-early gene (short) isoforms of Homer1 in the nucleus accumbens, withdrawal from repeated cocaine administration downregulates the expression of constitutive Homer1 isoforms. The present study determined whether or not this downregulation in constitutive Homer expression in the accumbens is necessary for enduring alterations in cocaine-induced changes in the brain and behavior. The long vs short Homer isoforms were overexpressed in the rat nucleus accumbens during drug abstinence, and the adaptations elicited by repeated cocaine on glutamate transmission and motor behavior were measured. It was found that both chronic and acute overexpression of constitutive, but not short, Homer isoforms abolished cocaine-induced sensitization of locomotor hyperactivity and prevented the development of glutamate abnormalities in the accumbens, including the reduction in basal extracellular glutamate content and the sensitized glutamate response to a subsequent cocaine challenge injection. Together, these data indicate that the enduring reduction of long Homer isoforms in the nucleus accumbens of cocaine-withdrawn rats is necessary for the expression of cocaine-induced neuroplasticity.

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Homer 1a Gene Expression Modulation by Antipsychotic Drugs Involvement of the Glutamate Metabotropic System and Effects of D-Cycloserine

Cited by 61 publications

References 34 publications

Chronic Olanzapine Treatment Causes Differential Expression of Genes in Frontal Cortex of Rats as Revealed by DNA Microarray Technique

Chronic Olanzapine Treatment Causes Differential Expression of Genes in Frontal Cortex of Rats as Revealed by DNA Microarray Technique

ADX47273 [S-(4-Fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: A Novel Metabotropic Glutamate Receptor 5-Selective Positive Allosteric Modulator with Preclinical Antipsychotic-Like and Procognitive Activities

Homer Isoforms Differentially Regulate Cocaine-Induced Neuroplasticity

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