Heat Shock Proteins Used to Show that Haloperidol Prevents Neuronal Injury Produced by Ketamine, MK801, and Phencyclidine<sup>a</sup>

Sharp, Frank R.; Butman, M.; Wang, Shu; Koistinaho, Jari; Graham, Steven H.; Sagar, Stephen M.; Berger, Paul; Longo, Frank M.

doi:10.1111/j.1749-6632.1993.tb18310.x

Cited by 11 publications

(6 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fluoro-Jadestained neurons are also evident in retrosplenial and posterior cingulate cortices of animals treated with MK-801, whether or not m-AMPH was also administered (Schmued et al, 1997, and present results). These findings are consistent with other evidence for cell degeneration in retrosplenial and posterior cingulate cortices of animals after administration of MK-801 or other noncompetitive NMDA receptor antagonists (Olney et al, 1989;Sharp et al, 1993).…”

Section: Discussionsupporting

confidence: 91%

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Eisch

Marshall

1998

Synapse

104

View full text Add to dashboard Cite

Methamphetamine (m-AMPH) administration injures both striatal dopaminergic terminals and certain nonmonoaminergic cortical neurons. Fluoro-Jade histochemistry was used to label cortical cells injured by m-AMPH in order to identify factors that contribute to the cortical cell body damage. Rats given four injections of m-AMPH (4 mg/kg) at 2-h intervals showed hyperthermia (mean = 40.0 +/- 0.10 degrees C) and increased behavioral activation relative to animals given saline (SAL). Three days later, m-AMPH-treated animals showed indices of injury to striatal DA terminals (depletion of tyrosine hydroxylase immunoreactivity) and parietal cortical cell bodies (appearance of Fluoro-Jade stained cells). Pretreatment with a dopamine (DA) D1, D2, or N-methyl-D-aspartate (NMDA) receptor antagonist, or administration of m-AMPH in a 4 degrees C environment, prevented or attenuated m-AMPH-induced hyperthermia, behavioral activation, and injury to striatal DA terminals and parietal cortical cell bodies. Animals pretreated with a DA transport inhibitor prior to m-AMPH showed hyperthermia, behavioral activation, and parietal cortical cell body injury, but they did not show striatal DA terminal injury. Pretreatment with a 5HT transport inhibitor failed to prevent m-AMPH-induced damage to striatal DA terminals or parietal cortical cell bodies. Animals given four injections of SAL in a 37 degrees C environment became hyperthermic, but showed no injury to striatal DA terminals or cortical cell bodies. The ability of the DA transport inhibitor to block m-AMPH-induced striatal DA damage, but not cortical injury, and the inability of hyperthermia alone to cause the cortical cell body injury suggests that m-AMPH-induced behavioral activation and hyperthermia may both be necessary for the subsequent parietal cortical cell body damage.

show abstract

Section: Discussionsupporting

confidence: 91%

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Eisch

Marshall

1998

Synapse

104

View full text Add to dashboard Cite

show abstract

“…Haloperidol blocked the injury to retrosplenial cortex produced by NMDA-receptor antagonists in rats (Sharp et al, 1992(Sharp et al, , 1993(Sharp et al, , 1994a. These findings prompted studies of atypical antipsychotics, including clozapine and olanzapine, which also blocked the cortical injury produced by NMDA antagonists in rodents (Farber et al, 1993(Farber et al, , 1996Olney and Farber, 1994;Sharp et al, 1994b).…”

Section: Introductionmentioning

confidence: 99%

Atypical Antipsychotics and a Src Kinase Inhibitor (PP1) Prevent Cortical Injury Produced by the Psychomimetic, Noncompetitive NMDA Receptor Antagonist MK-801

Dickerson

Sharp

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine, ketamine, and MK-801 produce schizophrenia-like psychosis in humans. The same NMDA antagonists injure retrosplenial cortical neurons in adult rats. We examined the effects of atypical antipsychotics and an inhibitor of nonreceptor tyrosine kinase pp60 (Src) on the cortical injury produced by MK-801. An atypical antipsychotic (either clozapine, ziprasidone, olanzapine, quetiapine, or risperidone) or vehicle was administered to adult female Sprague-Dawley rats. PP1 (Src inhibitor), PP3 (nonfunctional analog of PP1) or vehicle (DMSO) was administered to another group of animals. After pretreatment, animals were injected with MK-801, killed 24 h after the MK-801, and injury to retrosplenial cortex assessed by neuronal Hsp70 protein expression. All atypical antipsychotics examined significantly attenuated MK-801-induced cortical damage. PP1 protected compared to vehicle, whereas PP3 did not protect. The ED50s (decrease injury by 50%) were as follows: PP1 o0.1 mg/kg; olanzapine 0.8 mg/kg; risperdal 1 mg/kg; clozapine 3 mg/kg; ziprasidone 32 mg/kg; and quetiapine 45 mg/kg. The data show that the atypical antipsychotics tested as well as a Src kinase inhibitor prevent the injury produced by the psychomimetic MK-801, and the potency of the atypical antipsychotics for preventing cortical injury was roughly similar to the potency of these drugs for treating psychosis in patients.

show abstract

“…Indeed, drugs that decrease psychosis in people, including haloperidol and clozapine, prevent the cortical injury in rats produced by NMDA antagonists (Sharp et al . 1992, 1993, 1994; Farber et al . 1993; Olney 1994).…”

Section: Introductionmentioning

confidence: 99%

Bilateral blockade of NMDA receptors in anterior thalamus by dizocilpine (MK‐801) injures pyramidal neurons in rat retrosplenial cortex

Tomitaka

Tolliver

et al. 2000

Eur J of Neuroscience

Self Cite

View full text Add to dashboard Cite

Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine, phencyclidine (PCP) and dizocilpine (MK-801), produce psychosis in people. In rodents they produce cytoplasmic vacuoles in injured retrosplenial cortical neurons that express HSP70 heat shock protein. This study examined possible circuits and receptors that mediate this neuronal injury. Bilateral, but not unilateral, injection of dizocilpine (5, 10, 15, 20 microg/microL per side) into the anterior thalamus induced HSP70 protein in pyramidal neurons in deep layer III of rat retrosplenial cortex 24 h later. In contrast, bilateral dizocilpine injections (5, 10, 15, 20 microg/microL per side) into the retrosplenial cortex or into the diagonal band of Broca did not induce HSP70. Bilateral injections of muscimol (0.1, 1, 10 microg/microL per side), a GABAA (gamma-aminobutyric acid) agonist, into the anterior thalamus blocked HSP70 induction in the retrosplenial cortex produced by systemic dizocilpine (1 mg/kg). Bilateral thalamic injections of baclofen (0.1, 1, 10 microg/microL per side), a GABAB agonist, were ineffective. Anterograde tracer studies confirmed that neurons in the anterior thalamus project to superficial layer III of the retrosplenial cortex where the dendrites of HSP70-immunostained neurons in deep layer III reside. Bilateral blockade of NMDA receptors on GABA neurons in the reticular nuclei of the thalamus is proposed to decrease GABA neuronal firing, decrease GABA release and decrease activation of GABAA receptors. This activates thalamic projection neurons that damage retrosplenial cortical neurons presumably via unblocked cortical glutamate alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and kainate receptors. The increases of blood flow that occur in the thalamus and retrosplenial cortex of people that have psychosis produced by NMDA antagonists could be related to thalamic excitation of the retrosplenial cortex produced by these drugs.

show abstract

Heat Shock Proteins Used to Show that Haloperidol Prevents Neuronal Injury Produced by Ketamine, MK801, and Phencyclidine^a

Cited by 11 publications

References 8 publications

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Atypical Antipsychotics and a Src Kinase Inhibitor (PP1) Prevent Cortical Injury Produced by the Psychomimetic, Noncompetitive NMDA Receptor Antagonist MK-801

Bilateral blockade of NMDA receptors in anterior thalamus by dizocilpine (MK‐801) injures pyramidal neurons in rat retrosplenial cortex

Contact Info

Product

Resources

About

Heat Shock Proteins Used to Show that Haloperidol Prevents Neuronal Injury Produced by Ketamine, MK801, and Phencyclidinea

Cited by 11 publications

References 8 publications

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Methamphetamine neurotoxicity: Dissociation of striatal dopamine terminal damage from parietal cortical cell body injury

Atypical Antipsychotics and a Src Kinase Inhibitor (PP1) Prevent Cortical Injury Produced by the Psychomimetic, Noncompetitive NMDA Receptor Antagonist MK-801

Bilateral blockade of NMDA receptors in anterior thalamus by dizocilpine (MK‐801) injures pyramidal neurons in rat retrosplenial cortex

Contact Info

Product

Resources

About

Heat Shock Proteins Used to Show that Haloperidol Prevents Neuronal Injury Produced by Ketamine, MK801, and Phencyclidine^a