Interactions Between Monoamines, Glutamate, and GABA in Schizophrenia: New Evidence

Carlsson, Arvid; Waters, Nicholas; Holm-Waters, Susanna; Tedroff, Joakim; Nilsson, Mikael; Carlsson, Maria

doi:10.1146/annurev.pharmtox.41.1.237

Cited by 632 publications

(408 citation statements)

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“…This regulatory adaptation would mean that prefrontal glutamate transmission is deficient, while subcortical DA transmission is overactive. 10 This model provides a possible explanation for our observation that the augmented locomotor response to PCP in Nurr1 heterozygous ( þ /À) mice is mediated by changes in subcortical and cortical DA and NMDA transmission, respectively. Taken together, the Nurr1 ( þ /À) mice display an exaggerated locomotor responses to the psychostimulants/hallucinogens AMPH and PCP, consistent with animal models of schizophrenia.…”

Section: Discussionmentioning

confidence: 84%

“…DAergic hyperactivity has been the major hypothesis explaining the pathophysiology of schizophrenia involving disturbed DA transmission in mesolimbic and mesocortical pathways. 10 However, the neurochemical correlates to schizophrenia related to the DA hypothesis have remained elusive. Measurements of DA levels and DA receptor densities in postmortem schizophrenic brains have not provided any clear evidences for increases for DA transmission or DA D 2 receptors in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

“…9 Glutamate and DA, which share common postsynaptic targets, are believed to interact in a reciprocal manner at both cortical and subcortical structures. 10 Thus, a reduction in DA transmission may act to balance a glutamatergic insufficiency in schizophrenia. 10 Some of the symptoms in schizophrenia appear to involve disturbances in NMDA receptor function in the pFCx, probably mediated via alterations in DA receptor activity.…”

Section: Introductionmentioning

confidence: 99%

“…10 Thus, a reduction in DA transmission may act to balance a glutamatergic insufficiency in schizophrenia. 10 Some of the symptoms in schizophrenia appear to involve disturbances in NMDA receptor function in the pFCx, probably mediated via alterations in DA receptor activity. 8,11 Interestingly the noncompetitive NMDA antagonist phencyclidine (PCP) has been shown to induce both positive and negative schizophrenic symptoms as well as cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

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Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

et al. 2007

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The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous ( þ /À) male and female mice expressing 35-40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 ( þ /À) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 ( þ /À) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 ( þ /À) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 ( þ /À) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurr1 mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

et al. 2007

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“…Withdrawal from PCP treatment induces in humans and rodents some longlasting behavioral and neurochemical perturbations that have been hypothesized to have relevance to schizophrenia symptomatology and neuropathologies, respectively (Jentsch and Roth, 1999). These observations have led to the hypothesis of hypofunctioning of the glutamatergic system as one of the pathophysiologies mediating schizophrenia (Javitt and Zukin, 1991;Carlsson et al, 2001). The purpose of the present study was to test the hypothesis that withdrawal from PCP administration results in elevations in brain reward thresholds.…”

Section: Introductionmentioning

confidence: 94%

Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Spielewoy

Markou

2002

Neuropsychopharmacol

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Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/ kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

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