Ethanol Attenuates Spatial Memory Deficits and Increases mGlu1a Receptor Expression in the Hippocampus of Rats Exposed to Prenatal Stress

Authors

  • Vincent Van Waes,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Mihaela Enache,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Annarita Zuena,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Jérôme Mairesse,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Ferdinando Nicoletti,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Elisabeth Vinner,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Michel Lhermitte,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Stefania Maccari,

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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  • Muriel Darnaudéry

    1. From the NEUROSTRESS EA 4347, “Université Lille Nord de France” (VVW, ME, AZ, JM, SM, MD), 59655 Villeneuve d’Ascq, France; Department of Human Physio & Pharmacology, Sapienza University of Roma (AZ, JM, FN, SM), 00185 Roma, Italy; Neuromed (I.R.C.C.S.), 86079 Venafro (FN), Italy; and Laboratory of Toxicology & Genopathy UPRES EA 2679, “Université Lille Nord de France” (EV, ML) and Calmette Hospital, 59037 Lille, France.
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Reprint requests: Prof. Stefania Maccari, PhD, NEUROSTRESS EA4347, “Université Lille Nord de France,” University of Lille 1, 59655, Villeneuve d’Ascq, France; Fax: +33 3 20434602/+39 0649912524; E-mail: stefania.maccari@univ-lille1.fr and Visiting Professor Sapienza University of Rome, Italy

Abstract

Background:  Although it is generally believed that chronic ethanol consumption impairs learning and memory, results obtained in experimental animals are not univocal, and there are conditions in which ethanol paradoxically improves cognitive functions. In the present work, we investigated the effects of prenatal stress and of chronic ethanol exposure during adulthood on spatial memory in rats.

Methods:  Rats were subjected to a prenatal stress delivered as 3 daily 45-minute sections of restraint stress to the mothers during the last 10 days of pregnancy (PRS rats). After 7 months of ethanol exposure (ethanol 10%, oral intake), memory performances were evaluated in a spatial discrimination test in control and PRS male rats. Then, the oxidative damages and the expression of metabotropic glutamate (mGlu) receptors were assessed in their hippocampus.

Results:  Chronic ethanol exposure resulted in a reduced performance in a spatial recognition task in control animals. Unexpectedly, however, the same treatment attenuated spatial memory deficits in rats that had been subjected to prenatal stress. This paradigm of ethanol administration did not produce detectable signs of oxidative damage in the hippocampus in either unstressed or PRS rats. Interestingly, ethanol intake resulted in differential effects in the expression of mGlu receptor subtypes implicated in mechanisms of learning and memory. In control rats, ethanol intake reduced mGlu2/3 and mGlu5 receptor levels in the hippocampus; in PRS rats, which exhibited a constitutive reduction in the levels of these mGlu receptor subtypes, ethanol increased the expression of mGlu1a receptors but did not change the expression of mGlu2/3 or mGlu5 receptors.

Conclusion:  Our findings support the idea that stress-related events occurring before birth have long-lasting effects on brain function and behavior, and suggest that the impact of ethanol on cognition is not only dose- and duration-dependent, but also critically influenced by early life experiences.

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