Tritiated LSD Binding in Frontal Cortex in Schizophrenia

Whitaker, Patricia M.

doi:10.1001/archpsyc.1981.01780280046004

Cited by 124 publications

(37 citation statements)

References 14 publications

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“…WTSH and WTEE mice spent more time in the target quadrant than the other quadrants ( Figure 1b; F (1,32) = 8.4, P < 0.001 for WTSH and F (3,36) = 11.9, P < 0.001 for WTEE). KOSH and KOEE animals showed no preference for the quadrant in which the platform was located.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, in this study we present our characterization of the phenotype of the PLC-b1 KO mice, including behavioral paradigms assessing endophenotypes representative of aspects of schizophrenia symptomatology, 30,31 under different environmental and pharmacological conditions. In addition, we have examined whether key markers in the dopaminergic, serotonergic and cholinergic pathways, which have been shown to be altered in the cortex of subjects with schizophrenia, 17,[32][33][34][35][36][37][38] are altered by the PLC-b1 mutation or environmental stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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Phospholipase C-b1 (PLC-b1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-b1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-b1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenialike symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-b1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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“…Finally, post-mortem studies suggest a serotonergic dysfunction in cortical areas in schizophrenia. Eleven (Arora and Meltzer, 1991;Bennett, 1979;Burnet et al, 1996;Dean et al, 1998Dean et al, , 1999Gurevich and Joyce, 1997;Laruelle et al, 1993;Matsumoto et al, 2005;Mita et al, 1986;Pralong et al, 2000) out of 15 Joyce et al, 1993;Reynolds et al, 1983;Whitaker et al, 1981) post-mortem studies of brains of schizophrenic patients have reported decreased 5-HT 2A/C density in cortical areas, especially in the frontal cortex. Only two studies have addressed the subcortical 5-HT 2A density in post-mortem material: Joyce et al (1993) found an increased 5-HT 2A density in the ventral putamen and nucleus accumbens, whereas Matsumoto et al (2005) reported no significant difference in striatum between controls and patients suffering from schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

Erritzoe

Rasmussen

Kristiansen

et al. 2008

Neuropsychopharmacol

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The serotonin 5-HT 2A receptor is suspected to be involved in a number of psychiatric disorders, including schizophrenia. In particular, atypical antipsychotics have antagonistic effects on the 5-HT 2A receptors, supporting a specific role of the 5-HT 2A receptor in the pathophysiology of this disease. The aim of this study is to investigate cortical and subcortical 5-HT 2A binding in neuroleptic-naive schizophrenic patients. Fifteen neuroleptic-naive patients diagnosed with schizophrenia (age 27.5 ± 4.5 years), 11 men and 4 women, and 15 healthy control subjects matched for age (28.5 ± 5.7 years) and gender underwent a 40 min positron emission tomography (PET) study using the 5-HT 2A antagonist, [18 F]altanserin, as a radioligand. PET images were co-registered to 3 T magnetic resonance images (MRIs) for each individual subject, and ROIs were applied automatically onto the individual MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP p ) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT 2A receptor binding in the caudate nucleus was detected in the group of schizophrenic patients (0.7 ± 0.1) when compared to the healthy controls (0.5 ± 0.3) (p ¼ 0.02). Our results confirm other in vivo findings of no difference in cortical 5-HT 2A receptor binding between first-episode antipsychotic-naive schizophrenic patients and age-and gender-matched healthy control subjects. However, a preliminary finding of increased 5-HT 2A binding in the caudate nucleus requires further investigation to explore the relation of subcortical and cortical 5-HT 2A receptor binding.

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“…How ever, the results are controversial. Increased (Whitaker et al 1981), decreased (Bennett et al 1979;Mita et al 1986;Arora and Meltzer 1991;Laruelle et al 1991) or normal (Mackay et al 1978;Owen et al 1981;Reynolds et al 1983) 5-HT2 binding has been reported in the frontal cortex of neuroleptic-treated schizophrenic pa tients. Because neuroleptic drugs may downregulate 5-HT2 receptors in rodent brain (Andree et al 1986;Lee and Tang 1984), these results could be influenced by neuroleptic treatment.…”

mentioning

confidence: 95%

Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

Arora

Meltzer

1994

Neuropsychopharmacol

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Tritiated LSD Binding in Frontal Cortex in Schizophrenia

Cited by 124 publications

References 14 publications

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

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