Increased dopamine transmission in schizophrenia: relationship to illness phases

Laruelle, Marc; Abi‐Dargham, Anissa; Gil, Roberto; Kegeles, Lawrence S.; Innis, Robert B.

doi:10.1016/s0006-3223(99)00067-0

Cited by 640 publications

(397 citation statements)

References 92 publications

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“…33,34 Moreover, both dopamine receptor agonists and NMDA receptor antagonists can produce psychosis-like states in healthy human subjects and exacerbate existing psychoses in schizophrenics. [45][46][47][48][49] Interestingly, increased response to acute AMPH treatment has been directly implicated in the positive symptoms of schizophrenia, 47 whereas acute pharmacological treatment with NMDA receptor antagonists may additionally induce memory impairments related to the cognitive symptoms of schizophrenia. 50, 51 Prenatal immune activation by the inflammatory agent PolyI:C in mice thus precipitates a wide spectrum of adult behavioral and pharmacological abnormalities related especially to the symptom profiles in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

et al. 2007

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Maternal infections during pregnancy increase the risk for schizophrenia and related disorders of putative neurodevelopmental origin in the offspring. This association has been attributed to enhanced expression of pro-inflammatory cytokines in the fetal environment in response to maternal immunological stimulation. In contrast, the specific roles of anti-inflammatory cytokines are virtually unknown in this context. Here, we demonstrate that genetically enforced expression of the anti-inflammatory cytokine interleukin (IL)-10 by macrophages attenuates the long-term behavioral and pharmacological consequences of prenatal immune activation in a mouse model of prenatal viral-like infection by polyriboinosinic-polyribocytidilic acid (PolyI:C; 2 mg/kg, intravenously). In the absence of a discrete prenatal inflammatory stimulus, however, enhanced levels of IL-10 at the maternal-fetal interface by itself also precipitates specific behavioral abnormalities in the grown offspring. This highlights that in addition to the disruptive effects of excess pro-inflammatory molecules, a shift toward enhanced antiinflammatory signaling in prenatal life can similarly affect cognitive and behavioral development. Hence, shifts of the balance between pro-and anti-inflammatory cytokine classes may be a critical determinant of the final impact on neurodevelopment following early life infection or innate immune imbalances.

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Section: Discussionmentioning

confidence: 99%

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

et al. 2007

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“…In schizophrenic patients, increases in striatal DA release have generally been associated with the presence of positive symptoms (Laruelle et al, 1996(Laruelle et al, , 1999Abi-Dargham et al, 1998). However, the genetic liability for schizophrenia is thought to be better indexed by negative than positive symptom schizotypy (Tsuang et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Soliman

O’Driscoll

Pruessner

et al. 2007

Neuropsychopharmacol

129

106

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Drugs that increase dopamine levels in the brain can cause psychotic symptoms in healthy individuals and worsen them in schizophrenic patients. Psychological stress also increases dopamine release and is thought to play a role in susceptibility to psychotic illness. We hypothesized that healthy individuals at elevated risk of developing psychosis would show greater striatal dopamine release than controls in response to stress. Using positron emission tomography and [ 11 C]raclopride, we measured changes in synaptic dopamine concentrations in 10 controls and 16 psychometric schizotypes; 9 with perceptual aberrations (PerAb, ie positive schizotypy) and 7 with physical anhedonia (PhysAn, ie negative schizotypy). [ 11 C]Raclopride binding potential was measured during a psychological stress task and a sensory-motor control. All three groups showed significant increases in self-reported stress and cortisol levels between the stress and control conditions. However, only the PhysAn group showed significant stress-induced dopamine release. Dopamine release in the entire sample was significantly negatively correlated with smooth pursuit gain, an endophenotype linked to frontal lobe function. Our findings suggest the presence of abnormalities in the dopamine response to stress in negative symptom schizotypy, and provide indirect evidence of a link to frontal function.

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“…Further, dopamine (D2) receptor antagonists are therapeutically antipsychotic. This model has been supported recently by in vivo neuroimaging studies showing enhanced subcortical dopamine release in response to amphetamine challenge in individuals with schizophrenia (Abi-Dargham et al, 1998;Breier et al, 1997;Laruelle, 1998;Laruelle et al, 1996Laruelle et al, , 1999. However, amphetamine-induced responses exacerbate only the positive symptoms of schizophrenia.…”

Section: Introductionmentioning

confidence: 86%

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

Balla

Sershen

Serra

et al. 2003

Neuropsychopharmacol

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Functional dopaminergic hyperactivity is a key feature of schizophrenia. Etiology of this dopaminergic hyperactivity, however, is unknown. We have recently demonstrated that subchronic phencyclidine (PCP) treatment in rodents induces striatal dopaminergic hyperactivity similar to that observed in schizophrenia. The present study investigates the ability of PCP to potentiate amphetamine-induced dopamine release in prefrontal cortex (PFC) and nucleus accumbens (NAc) shell. Prefrontal dopaminergic hyperactivity is postulated to underlie cognitive dysfunction in schizophrenia. In contrast, the degree of NAc involvement is unknown and recent studies have suggested that PCP-induced hyperactivity in rodents may correlate with PFC, rather than NAc, dopamine levels. Rats were treated with 5-20 mg/kg/day PCP for 3-14 days by osmotic minipump. PFC and NAc dopamine release to amphetamine challenge (1 mg/kg) was monitored by in vivo microdialysis and HPLC-EC. Doses of 10 mg/kg/day and above produced serum PCP concentrations (50-150 ng/ml) most associated with PCP psychosis in humans. PCP-treated rats showed significant, dose-dependent enhancement in amphetamine-induced dopamine release in PFC but not NAc, along with significantly enhanced locomotor activity. Enhanced response was observed following 3-day, as well as 14-day, treatment and resolved within 4 days of PCP treatment withdrawal. These findings support the concept that endogenous NMDA receptor dysfunction could account for the pattern of dopaminergic dysfunction observed in schizophrenia, and suggest that even short duration abuse of PCP-like agents may greatly potentiate behavioral effects of psychostimulants in drug abuse situations. Finally, these studies provide a model system in which to evaluate effects of potential psychotherapeutic agents.

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Increased dopamine transmission in schizophrenia: relationship to illness phases

Cited by 640 publications

References 92 publications

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

Subchronic Continuous Phencyclidine Administration Potentiates Amphetamine-Induced Frontal Cortex Dopamine Release

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