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Molecular Pharmacology

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Research ArticleArticle

Early Life Stress Causes Refractoriness to Haloperidol-Induced Catalepsy

Jordan Marrocco, Jérôme Mairesse, Domenico Bucci, Luana Lionetto, Giuseppe Battaglia, Michol Consolazione, Laura Ravasi, Maurizio Simmaco, Sara Morley-Fletcher, Stefania Maccari and Ferdinando Nicoletti
Molecular Pharmacology August 2013, 84 (2) 244-251; DOI: https://doi.org/10.1124/mol.113.085530
Jordan Marrocco
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Jérôme Mairesse
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Domenico Bucci
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Luana Lionetto
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Giuseppe Battaglia
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Michol Consolazione
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Laura Ravasi
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Maurizio Simmaco
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Sara Morley-Fletcher
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Stefania Maccari
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Ferdinando Nicoletti
IRCCS Centro Neurolesi “Bonino Pulejo,” Messina, Italy (Jo.M.); Neural Plasticity Team—UMR CNRS/USTL no. 8576 Structural and Functional Glycobiology Unit, North University of Lille, France (Jé.M., M.C., S.M.-F., S.M.); IRCCS Neuromed, Pozzilli, Italy (D.B., G.B., F.N.); EA1046, IMPRT-IFR114, Faculty of Medicine, North University of Lille, France (L.R.); and Department of Neuroscience, Mental Health and Sensory Organs, Advanced Molecular Diagnostics, St. Andrea Hospital (L.L., M.S.), and Department of Physiology and Pharmacology (F.N.), Sapienza University of Rome, Italy
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Abstract

The use of classic antipsychotic drugs is limited by the occurrence of extrapyramidal motor symptoms, which are caused by dopamine (DA) receptor blockade in the neostriatum. We examined the impact of early-life stress on haloperidol-induced catalepsy using the rat model of prenatal restraint stress (PRS). Adult “PRS rats,” i.e., the offspring of mothers exposed to restraint stress during pregnancy, were resistant to catalepsy induced by haloperidol (0.5–5 mg/kg i.p.) or raclopride (2 mg/kg s.c.). Resistance to catalepsy in PRS rats did not depend on reductions in blood or striatal levels, as compared with unstressed control rats. PRS rats also showed a greater behavioral response to the DA receptor agonist, apomorphine, suggesting that PRS causes enduring neuroplastic changes in the basal ganglia motor circuit. To examine the activity of this circuit, we performed a stereological counting of c-Fos+ neurons in the external and internal globus pallidus, subthalamic nucleus, and ventral motor thalamic nuclei. Remarkably, the number of c-Fos+ neurons in ventral motor thalamic nuclei was higher in PRS rats than in unstressed controls, both under basal conditions and in response to single or repeated injections with haloperidol. Ventral motor thalamic nuclei contain exclusively excitatory projection neurons that convey the basal ganglia motor programming to the cerebral cortex. Hence, an increased activity of ventral motor thalamic nuclei nicely explains the refractoriness of PRS rats to haloperidol-induced catalepsy. Our data raise the interesting possibility that early-life stress is protective against extrapyramidal motor effects of antipsychotic drugs in the adult life.

Footnotes

    • Received February 8, 2013.
    • Accepted May 28, 2013.
  • This study was supported by the North of France University of Lille-Lille1 and the Sapienza University of Rome (Frame Agreement signed between the two universities on 15/02/2007); and by CNRS in the framework of the European Research Team (GDRE 691) “Early Programming of Modern Diseases.”

  • dx.doi.org/10.1124/mol.113.085530.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 84 (2)
Molecular Pharmacology
Vol. 84, Issue 2
1 Aug 2013
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Research ArticleArticle

Prenatal Stress and Antipsychotic Drug-Induced Parkinsonism

Jordan Marrocco, Jérôme Mairesse, Domenico Bucci, Luana Lionetto, Giuseppe Battaglia, Michol Consolazione, Laura Ravasi, Maurizio Simmaco, Sara Morley-Fletcher, Stefania Maccari and Ferdinando Nicoletti
Molecular Pharmacology August 1, 2013, 84 (2) 244-251; DOI: https://doi.org/10.1124/mol.113.085530

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Research ArticleArticle

Prenatal Stress and Antipsychotic Drug-Induced Parkinsonism

Jordan Marrocco, Jérôme Mairesse, Domenico Bucci, Luana Lionetto, Giuseppe Battaglia, Michol Consolazione, Laura Ravasi, Maurizio Simmaco, Sara Morley-Fletcher, Stefania Maccari and Ferdinando Nicoletti
Molecular Pharmacology August 1, 2013, 84 (2) 244-251; DOI: https://doi.org/10.1124/mol.113.085530
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