Chronic haloperidol, but not clozapine, produces altered oral movements and increased extracellular glutamate in rats

See, Ronald E.; Chapman, Mary Ann

doi:10.1016/0014-2999(94)90722-6

Cited by 76 publications

(46 citation statements)

References 41 publications

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“…It has recently been shown that 6-OHDA lesion of the nigrostriatal pathway causes decreased GLU immunolabeling and increased extracellular levels of GLU in the striatum as measured by microdialysis (Meshul et al, 1997). In addition, 1 day following 4 weeks of haloperidol treatment a decrease in nerve terminal GLU immunolabeling (Meshul et al, 1995) and an increase in the basal extracellular levels of striatal GLU (See and Chapman, 1994;Yamamoto and Cooperman, 1994) were observed. These studies suggest an inverse relationship between terminal immunolabeling and extracellular levels of GLU.…”

Section: Discussionmentioning

confidence: 94%

Reduced glutamate immunolabeling in the nucleus accumbens following extended withdrawal from self-administered cocaine

Keys

Mark

Emre³

et al. 1998

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Alterations in the density of GABA and glutamate immunolabeling within nerve terminals in the shell region of the nucleus accumbens were assessed in rats withdrawn from intravenous cocaine exposure. Four groups of rats were used: one group self-administered cocaine (0.42 mg/kg/infusion) in daily 3-h sessions for approximately 2 weeks, two additional groups received either saline or cocaine in a noncontingent fashion, and a fourth comprised a drug-naive, age-matched control group. Immunogold electron microscopy was used to quantify presynaptic terminal GABA and glutamate density within the vesicular and mitochondrial pools approximately 18 days following the last drug or saline exposure in the treatment groups. A significant 27.7% decrease in vesicular glutamate density within asymmetrical nerve terminals was observed in animals that self-administered cocaine as compared to controls. This group also showed an 18.6% decrease in vesicular nerve terminal glutamate immunolabeling as compared to animals that were administered a similar total dose of cocaine in a response-independent fashion. No significant changes in the density of nerve terminal GABA vesicular immunolabeling were observed in any groups. For both transmitters, no differences were detected in the density of immunolabeling within the presynaptic mitochondrial (i.e., metabolic) pool. These results demonstrate that glutamate density is suppressed in the shell region of the nucleus accumbens following withdrawal from 2 weeks of cocaine exposure. The findings also suggest that the motivational aspects that accompany self-administration may participate in this reduction.

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Section: Discussionmentioning

confidence: 94%

Reduced glutamate immunolabeling in the nucleus accumbens following extended withdrawal from self-administered cocaine

Keys

Mark

Emre³

et al. 1998

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“…When tested in rats, NMDA receptor antagonists produce behavioral responses that model schizophrenic symptoms and are blocked by antipsychotic drugs, including clozapine (e.g., Hauber 1993). Chronic administration of antipsychotic drugs alters glutamate receptor expression in rat brain (Chen et al 1998; Eastwood et al 1994 Eastwood et al , 1996 Fitzgerald et al 1995;Healy and Meador-Woodruff 1997;Riva et al 1997;Tascedda et al 1999) and alters EAA levels as measured by microdialysis (Daly and Moghaddam 1993;See and Chapman 1994;See and Lynch 1996;Yamamoto and Cooperman 1994).The ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) subtype of glutamate receptor mediates the majority of excitatory transmission in brain. Different combinations of four AMPA receptor subunits (GluR1-4) give rise to heteromeric receptors with distinct properties (Hollman and Heinemann, 1994).…”

mentioning

confidence: 99%

Expression of AMPA Receptor Flip and Flop mRNAs in the Nucleus Accumbens and Prefrontal Cortex after Neonatal Ventral Hippocampal Lesions

Stine

Wolf

2001

Neuropsychopharmacology

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Many lines of evidence implicate dysfunctional excitatory amino acid (EAA) transmission in schizophrenia. The present study examined ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) receptor expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) using a rat model of schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) on postnatal day (PD) 7 lead to the postpubertal emergence of behavioral abnormalities that resemble schizophrenic symptoms. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to quantify mRNA levels for respectively Recent hypotheses about the pathophysiology of schizophrenia have posited defects in excitatory amino acid (EAA) transmission (e.g., Carlsson and Carlsson 1990; Coyle 1996;Krystal et al. 1999;Olney and Farber 1995). A number of different lines of evidence support the involvement of EAAs. First, N-methyl-D-aspartate (NMDA) receptor antagonists produce effects in normal human subjects that resemble those associated with schizophrenia (Krystal et al. 1999). Second, schizophrenic brains exhibit abnormalities in glutamate metabolism (Bartha et al. 1997; Do et al. 1995; Faustman et al. 1999;Tsai et al. 1995) and glutamate receptor expression (reviewed by Meador-Woodruff and Healy 2000). Finally, drugs that alter glutamate transmission can ameliorate schizophrenic symptoms (Heresco-Levy et al. 1996;Javitt et al. 1994;Tsai et al. 1998 NO . 3 antipsychotic drug treatment alters EAA levels in the CSF and serum of schizophrenic patients (Evins et al. 1997;Labarca et al. 1995).Preclinical research also supports a role for EAAs in the pathogenesis of schizophrenia. When tested in rats, NMDA receptor antagonists produce behavioral responses that model schizophrenic symptoms and are blocked by antipsychotic drugs, including clozapine (e.g., Hauber 1993). Chronic administration of antipsychotic drugs alters glutamate receptor expression in rat brain (Chen et al. 1998; Eastwood et al. 1994 Eastwood et al. , 1996 Fitzgerald et al. 1995;Healy and Meador-Woodruff 1997;Riva et al. 1997;Tascedda et al. 1999) and alters EAA levels as measured by microdialysis (Daly and Moghaddam 1993;See and Chapman 1994;See and Lynch 1996;Yamamoto and Cooperman 1994).The ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) subtype of glutamate receptor mediates the majority of excitatory transmission in brain. Different combinations of four AMPA receptor subunits (GluR1-4) give rise to heteromeric receptors with distinct properties (Hollman and Heinemann, 1994). The purpose of the present study was to examine the possible role of alterations in AMPA receptor expression in schizophrenia, using a rat model for schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) are produced on postnatal day (PD) 7 . By interrupting connections between the limbic system and cortex during the vulnerable neonatal period, neonatal VH lesions may produce developmental changes related to those that are believed to underlie schizophre...

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“…In addition, the glutamatergic cortical projection neurons contain D 2 -dopamine receptor mRNA (Lidow et al, 1998) and show diminished striatal release of glutamate in the presence of D 2 -dopamine receptor agonists (Donzanti et al, 1993). Together, these observations suggest that haloperidol blockade of D 2 -dopamine receptors enhances postsynaptic response and/or presynaptic release of glutamate within the cortical projections to dendritic spines in the CPN (Moghaddam, 1994;See and Chapman, 1994;Yamamoto and Cooperman, 1994).…”

Section: Increased Nmdar1 Immunoreactivity In Dendritic Spines In Thementioning

confidence: 83%

“…The changes in density of glial processes following haloperidol administration may reflect changes not only in content of NMDAR1 in glia, but in size and/or shape of the glial processes. These changes might be attributed to increased basal glutamate release seen following haloperidol administration (Moghaddam, 1994;See and Chapman, 1994;Yamamoto and Cooperman, 1994). Binding of glutamate to NMDA receptors in striatal glia, together with opening of voltage-gated Ca 2ϩ channels, could significantly increase intracellular calcium levels, as has been shown in cultured O-2A glial progenitor cells (Steinhauser and Gallo, 1996).…”

Section: Decreased Nmdar1 Immunoreactivity In Gliamentioning

confidence: 94%

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

Rodrı́guez

Pickel

1999

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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.

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Chronic haloperidol, but not clozapine, produces altered oral movements and increased extracellular glutamate in rats

Cited by 76 publications

References 41 publications

Reduced glutamate immunolabeling in the nucleus accumbens following extended withdrawal from self-administered cocaine

Reduced glutamate immunolabeling in the nucleus accumbens following extended withdrawal from self-administered cocaine

Expression of AMPA Receptor Flip and Flop mRNAs in the Nucleus Accumbens and Prefrontal Cortex after Neonatal Ventral Hippocampal Lesions

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

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