Selective loss of cerebral cortical Sigma, but not PCP binding sites in schizophrenia

Weissman, Arthur D.; Casanova, Manuel F.; Kleinman, Joel E.; London, Edythe D.; Souza, Errol B. De

doi:10.1016/0006-3223(91)90209-5

Cited by 141 publications

(54 citation statements)

References 37 publications

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“…In the putamen, NMDA receptor numbers are elevated (Aparicio-Legarza et al, 1998;Kornhuber et al, 1989), and in the cortex, the number is increased and the composition of the NMDA receptor subunits is altered (Akbarian et al, 1996;Grimwood et al, 1999;Ishimaru et al, 1994;Nudmamud & Reynolds, 2001;Simpson et al, 1991). However, as might be expected from human post mortem studies, not all investigators found similar changes in the expression of ionotropic glutamate receptors in schizophrenia (Breese et al, 1995;Noga et al, 1997;Weissman et al, 1991). Nevertheless, several observations appear to be fairly consistent among different research groups.…”

Section: The Role Of Glutamate In Neurotoxicity-mentioning

confidence: 86%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

296

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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Section: The Role Of Glutamate In Neurotoxicity-mentioning

confidence: 86%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

296

165

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“…Secondly, because haloperidol and phencyclidine can bind to sigma-recep tors (37,38), but risperidone can not (35), it is possible that sigma-receptors may be involved in dopamine turn over. Recently, several investigators have demonstrated that sigma-receptors may play an important role in schizophrenia (37,39) and that some of the sigma-recep tor ligands have the ability to change dopamine turnover (40,41). Moreover, phencyclidine-induced head-weaving, which is partly mediated by nigrostriatal dopaminergic neuronal systems (29,30), was blocked by the sigma receptor antagonists NE-100 and BMY-14802 (42, 43) Therefore, it is possible that our present results may result from the differences in the binding affinity for sigma receptors between risperidone and haloperidol, although the roles of sigma-receptors on dopamine turnover remain to be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

Kitaichi

Yamada

Hasegawa

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-In this study, we investigated whether risperidone, a serotonin-S2A (5-HT21)/dopamine-D2 (D2)-receptor antagonist, inhibits phencyclidine (PCP)-induced stereotyped behaviors in comparison with haloperidol and ritanserin. Moreover, we also attempted to investigate the effects of these antipsychotics on the contents of dopamine, serotonin (5-HT) and their metabolites in rat striatum and frontal cortex. In rats, PCP (5 mg/kg, i.p.) caused hyperlocomotion and stereotyped behaviors, including sniffing, head-weaving, backpedalling and turning. Both risperidone (0.8-2.4 mg/kg, p.o.) and haloperidol (0.3-1.0 mg/kg, p.o.) inhibited these behaviors, except for backpedalling, in a dose-dependent manner. PCP (10 mg/kg, i.p.) pro duced hyperlocomotion and stereotyped behaviors, including rearing, sniffing head-twitch, backpedalling and turning. Risperidone (0.8-2.4 mg/kg, p.o.) inhibited both hyperlocomotion and PCP-induced behaviors, except for backpedalling, while ritanserin (3 -10 mg/kg, p.o.) inhibited only the head-twitch. These results suggest that risperidone may have an antipsychotic effect on schizophrenia as well as PCP psychosis in humans by exerting a mixed 5-HT2A/D2 antagonism. Neurochemically, the increasing effects of risperidone on the content of DOPAC and the ratio of DOPAC to dopamine in the striatum were lower than those of haloperidol. These findings may support the view that the extrapyramidal side effects of risperidone are lower than those of haloperidol in clinical situations.

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“…In addition, a recent post-mortem study found reduced densities of sigma receptors in brains of patients with schizophrenia (Weissman et al 1991). The function of the sigma receptor is not known; however, one study suggested that it is coupled to phos phoinositol turnover in peripheral tissues.…”

mentioning

confidence: 99%

BMY 14802, a Sigma Receptor Ligand for the Treatment of Schizophrenia

Gewirtz

Gorman

Volavka

et al. 1994

Neuropsychopharmacol

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Selective loss of cerebral cortical Sigma, but not PCP binding sites in schizophrenia

Cited by 141 publications

References 37 publications

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Effects of Risperidone on Phencyclidine-Induced Behaviors: Comparison with Haloperidol and Ritanserin

BMY 14802, a Sigma Receptor Ligand for the Treatment of Schizophrenia

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