Regulation of NMDA receptor subunit messenger RNA levels in the rat brain following acute and chronic exposure to antipsychotic drugs

Riva, Marco A.; Tascedda, Fabio; Lovati, E.; Racagni, Giorgio

doi:10.1016/s0169-328x(97)00175-7

Cited by 71 publications

(53 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Resultssupporting

confidence: 57%

“…Similarly the expression of NR-1, NR-2A, and NR-2B in the striatum was not altered and only a small, although significant, increase in the levels for NR-2C mRNA in this structure was detected. Conversely, chronic administration of quetiapine produced a significant reduction of NR-1 and NR-2C mRNA levels in the nucleus accumbens, an effect we had previously observed with clozapine but not classical neuroleptics (Riva et al 1997).Subsequently, we investigated, under the same experimental conditions, the expression profile for AMPA receptor subunits . We found that quetiapine, as well as haloperidol and clozapine, did not affect GluR-A, -B and -C mRNA levels in the striatum.…”

mentioning

confidence: 86%

“…The RNase protection assay was performed on a 10 g sample of total RNA as described previously (Riva et al 1997). Briefly, after ethanol-precipitation total RNA, obtained from different tissues, was dissolved in 20 l of hybridization solution (80% formamide; 40 mM PIPES, pH 6.4; 400 mM sodium acetate, pH 6.4; and 1 mM EDTA) containing 150,000 cpm of each 32 P-labeled cRNA probes (specific activity Ͼ 10 8 cpm/ g).…”

Section: Probe Preparation and Rnase Protection Assaymentioning

confidence: 99%

“…The cDNAs for the different NMDA or AMPA receptor subunits were arranged in order to obtain proper templates for the in vitro transcription of cRNA probes to be used in the RNase protection assay (Riva et al 1997). …”

Section: Probe Preparation and Rnase Protection Assaymentioning

confidence: 99%

“…Hence, on the basis of its functional interaction with dopamine, glutamate and Received September 15, 1998; revised February 15, 1999; accepted February 25, 1999. Recently, a number of different laboratories, including our own, have examined the regulation of glutamate receptors in response to treatment with haloperidol and clozapine (Fitzgerald et al 1995;Riva et al 1997;Healy and Meador-Woodruff 1997;Brené et al 1998). In the present study, we investigated the modulation of the mRNA encoding for NMDA and AMPA glutamate receptor subunits in response to the atypical antipsychotic drug "Seroquel (quetiapine fumarate, quetiapine)" (Goldstein 1996).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Regulation of Ionotropic Glutamate Receptors in the Rat Brain in Response to the Atypical Antipsychotic Seroquel (Quetiapine Fumarate)

Tascedda

Lovati

Blom

et al. 1999

Neuropsychopharmacology

View full text Add to dashboard Cite

In light of the knowledge accumulated during the past couple of decades, it is apparent that schizophrenia is a complex and heterogeneous disease (Lieberman and Koreen 1993). Even though, classical neuroleptics are clearly useful in the treatment of positive aspect of the disease, they have a limited efficacy on negative symptoms and cognitive deterioration (Meltzer 1991). Conversely, clozapine and the novel antipsychotics have been termed 'atypicals' because they have a lower incidence of extrapyramidal side effects and can be effective in the treatment of negative symptoms (Deutch et al. 1991;Kinon and Lieberman 1996).The molecular basis of these differences has not been clearly established, but could be related to receptor profiles, regional specificity within the CNS and the possibility to produce adaptive changes in specific neurotransmitter systems whose function is altered in schizophrenia (Ellenbroek 1993). Among the others, dopamine, glutamate, and their reciprocal interactions within discrete neuronal circuitry, can be viewed as major players in schizophrenia imbalance (Weinberger 1987;Carlsson and Carlsson 1990;DiChiara et al. 1994). Hyperdopaminergic activity is thought to be relevant for positive symptoms of the disease, whereas alterations in glutamatergic system could explain several features of the disorder including negative symptoms and cognitive dysfunctions (Olney and Farber 1995;Weinberger and Lipska 1995). Hence, on the basis of its functional interaction with dopamine, glutamate and Received September 15, 1998; revised February 15, 1999; accepted February 25, 1999. Recently, a number of different laboratories, including our own, have examined the regulation of glutamate receptors in response to treatment with haloperidol and clozapine (Fitzgerald et al. 1995;Riva et al. 1997;Healy and Meador-Woodruff 1997;Brené et al. 1998). In the present study, we investigated the modulation of the mRNA encoding for NMDA and AMPA glutamate receptor subunits in response to the atypical antipsychotic drug "Seroquel (quetiapine fumarate, quetiapine)" (Goldstein 1996).In order to gain insight in the possible relationships between the changes in glutamate receptor expression and the clinical properties of the drug, we have compared the effects elicited by quetiapine to those observed with haloperidol and clozapine, the prototypes for classical and atypical antipsychotics. MATERIALS AND METHODMale Sprague Dawley rats (Charles River, Calco, Italy) weighing 250-350 g were used throughout the experiments. The animals were maintained under a 12 hr light/12 hr dark cycle with food and water available ad libitum. Animals received daily subcutaneous injections with saline, haloperidol (1 mg/kg), clozapine (30 mg/ kg), or quetiapine (25 mg/kg) for 21 days. Rats were sacrificed by decapitation 6 hr after the last injection. The brain regions were rapidly dissected, frozen in liquid nitrogen, and stored at Ϫ 70 Њ C for further analysis. All animal manipulations have been carried out in accordance with the Guide for...

show abstract

Section: Resultssupporting

confidence: 57%

mentioning

confidence: 86%

Section: Probe Preparation and Rnase Protection Assaymentioning

confidence: 99%

Section: Probe Preparation and Rnase Protection Assaymentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Regulation of Ionotropic Glutamate Receptors in the Rat Brain in Response to the Atypical Antipsychotic Seroquel (Quetiapine Fumarate)

Tascedda

Lovati

Blom

et al. 1999

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

Enhancement of N-methyl-D-aspartate (NMDA) immunoreactivity in residual dendritic spines in the caudate-putamen nucleus after chronic haloperidol administration

Rodrı́guez

Pickel

1999

Synapse

View full text Add to dashboard Cite

Glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype in the caudate-putamen nucleus (CPN) have been implicated in the adverse motor effects produced by chronic administration of the typical antipsychotic drug haloperidol. To determine the functionally relevant sites, we examined the electron microscopic immunocytochemical localization of the R1 receptor subunit (NMDAR1) in the dorsolateral CPN of rats receiving 4 months of biweekly depot intramuscular injections of either haloperidol or vehicle. In all animals, NMDAR1 immunoreactivity was seen mainly in dendritic spines, but was also present in a few somata and dendrites of spiny neurons, axon terminals, and glia. In comparison with controls, the dissector stereological analysis showed a significant reduction in the numerical density of total NMDAR1-labeled and unlabeled dendritic spines in the dorsolateral CPN after haloperidol administration. When labeled spines were identified separately based exclusively on the presence of immunoreactivity within a single plane of section, there was, however, a significant increase in the numerical density of NMDAR1-containing spines in haloperidol vs. control animals. This increase was not seen using a classic dissector, suggesting that the enhancement was mainly attributed to more frequent detection of spines having higher levels of NMDA immunoreactivity. Our results are the first to identify dendritic spines in the dorsolateral CPN as preferential sites for the regulated expression of NMDA receptors following chronic administration of haloperidol.

show abstract

Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats

Spurney

Baca

Murray

et al. 1999

Synapse

View full text Add to dashboard Cite

Despite multiple lines of investigation the effect of neuroleptics on glutamate-mediated neurotransmission remains controversial. To study the effects of typical and atypical neuroleptics on selected parameters of glutamate-mediated neurotransmission, male Sprague-Dawley rats were randomly assigned to a 21-day oral treatment course with vehicle, haloperidol (HDL), or clozapine (CLZ). Coronal slices of rat brain were then incubated with tritiated ligands to measure NMDA, AMPA, and kainate receptor, and glutamate reuptake site density. Regions of interest included the frontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, and the nucleus accumbens. CLZ increased the density of AMPA receptors significantly in the frontal and anterior cingulate cortices compared with normal controls. In the dorsal and ventral striatum, and nucleus accumbens as a whole, CLZ-treated rats had a higher AMPA receptor density compared with both the HDL- and vehicle-treated controls. Additionally, within the nucleus accumbens, CLZ-treated rats had a higher density of AMPA receptors compared with the HDL group in the core, and at trend level in the shell. There was a group by region interaction for NMDA receptor density, primarily reflecting the tendency of HDL treated rats to have high receptor densities in the frontal and anterior cingulate cortices. Kainate receptors and glutamate reuptake site densities did not differ significantly across groups. These results suggest a critical role for glutamate in the mediation of atypical antipsychotic drug action in anatomically-specific regions, and further encourage the investigation of glutamate neurotransmitter systems in schizophrenia.

show abstract

Regulation of NMDA receptor subunit messenger RNA levels in the rat brain following acute and chronic exposure to antipsychotic drugs

Cited by 71 publications

References 33 publications

Regulation of Ionotropic Glutamate Receptors in the Rat Brain in Response to the Atypical Antipsychotic Seroquel (Quetiapine Fumarate)

Regulation of Ionotropic Glutamate Receptors in the Rat Brain in Response to the Atypical Antipsychotic Seroquel (Quetiapine Fumarate)

Enhancement of N-methyl-D-aspartate (NMDA) immunoreactivity in residual dendritic spines in the caudate-putamen nucleus after chronic haloperidol administration

Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats

Contact Info

Product

Resources

About