Maternal Immune Activation Disrupts Dopamine System in the Offspring

Antonio Luchicchi, Salvatore Lecca, Miriam Melis, Marta De Felice, Francesca Cadeddu, Roberto Frau, Anna Lisa Muntoni, Paola Fadda, Paola Devoto, Marco Pistis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia.

METHODS: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology.

RESULTS: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity.

CONCLUSIONS: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 2016
Externally publishedYes

Cite this

Luchicchi, Antonio ; Lecca, Salvatore ; Melis, Miriam ; De Felice, Marta ; Cadeddu, Francesca ; Frau, Roberto ; Muntoni, Anna Lisa ; Fadda, Paola ; Devoto, Paola ; Pistis, Marco. / Maternal Immune Activation Disrupts Dopamine System in the Offspring. In: International Journal of Neuropsychopharmacology. 2016 ; Vol. 19, No. 7.
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abstract = "BACKGROUND: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia.METHODS: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology.RESULTS: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity.CONCLUSIONS: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology.",
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Luchicchi, A, Lecca, S, Melis, M, De Felice, M, Cadeddu, F, Frau, R, Muntoni, AL, Fadda, P, Devoto, P & Pistis, M 2016, 'Maternal Immune Activation Disrupts Dopamine System in the Offspring' International Journal of Neuropsychopharmacology, vol. 19, no. 7. https://doi.org/10.1093/ijnp/pyw007

Maternal Immune Activation Disrupts Dopamine System in the Offspring. / Luchicchi, Antonio; Lecca, Salvatore; Melis, Miriam; De Felice, Marta; Cadeddu, Francesca; Frau, Roberto; Muntoni, Anna Lisa; Fadda, Paola; Devoto, Paola; Pistis, Marco.

In: International Journal of Neuropsychopharmacology, Vol. 19, No. 7, 07.2016.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Maternal Immune Activation Disrupts Dopamine System in the Offspring

AU - Luchicchi, Antonio

AU - Lecca, Salvatore

AU - Melis, Miriam

AU - De Felice, Marta

AU - Cadeddu, Francesca

AU - Frau, Roberto

AU - Muntoni, Anna Lisa

AU - Fadda, Paola

AU - Devoto, Paola

AU - Pistis, Marco

N1 - © The Author 2016. Published by Oxford University Press on behalf of CINP.

PY - 2016/7

Y1 - 2016/7

N2 - BACKGROUND: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia.METHODS: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology.RESULTS: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity.CONCLUSIONS: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology.

AB - BACKGROUND: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia.METHODS: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology.RESULTS: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity.CONCLUSIONS: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology.

KW - Journal Article

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DO - 10.1093/ijnp/pyw007

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VL - 19

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

SN - 1461-1457

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