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Ventral striatum regulates behavioral response to ethanol and MDMA combination.
Ben Hamida, Sami; Lecourtier, Lucas; Loureiro, Michaël; Cosquer, Brigitte; Tracqui, Antoine; Simmoneaux, Valérie; Nehlig, Astrid; Jones, Byron C; Pereira de Vasconcelos, Anne; Cassel, Jean-Christophe.
Afiliação
  • Ben Hamida S; Laboratoire de Neurosciences Cognitives et Adaptatives, LNCA, UMR7364-CNRS, Université de Strasbourg, Strasbourg, France.
  • Lecourtier L; Douglas Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Montréal, Quebec, Canada.
  • Loureiro M; Laboratoire de Neurosciences Cognitives et Adaptatives, LNCA, UMR7364-CNRS, Université de Strasbourg, Strasbourg, France.
  • Cosquer B; Laboratoire de Neurosciences Cognitives et Adaptatives, LNCA, UMR7364-CNRS, Université de Strasbourg, Strasbourg, France.
  • Tracqui A; Laboratoire de Neurosciences Cognitives et Adaptatives, LNCA, UMR7364-CNRS, Université de Strasbourg, Strasbourg, France.
  • Simmoneaux V; Service de Médecine Légale, Hôpital Saint-Jacques-CHRU, Besançon, France.
  • Nehlig A; INCI, Institut des Neurosciences Cellulaires et Intégratives, UPR 3212, CNRS, Université de Strasbourg, Strasbourg, France.
  • Jones BC; INSERM U1129, Pediatric Neurology Necker-Enfants Malades Hospital University of Paris Descartes, Paris, France.
  • Pereira de Vasconcelos A; The University of Tennessee Health Science Center, 77 South Manassas Street, Memphis, Tennessee, USA.
  • Cassel JC; Laboratoire de Neurosciences Cognitives et Adaptatives, LNCA, UMR7364-CNRS, Université de Strasbourg, Strasbourg, France.
Addict Biol ; 26(2): e12938, 2021 03.
Article em En | MEDLINE | ID: mdl-32666571
ABSTRACT
Our previous studies consistently showed that MDMA-induced locomotor hyperactivity is dramatically increased by coadministration of ethanol (EtOH) in rats, indicating possible potentiation of MDMA abuse liability. Thus, we aimed to identify the brain region(s) and neuropharmacological substrates involved in the pharmacodynamics of this potentiation. We first showed that potentiation of locomotor activity by the combination of ip administration of EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) is delay sensitive and maximal when both drugs are injected simultaneously. Then, we used the 2-deoxyglucose quantitative autoradiography technique to assess the impact of EtOH, MDMA, or their combination on local cerebral metabolic rates for glucose (CMRglcs). We showed a specific metabolic activation in the ventral striatum (VS) under MDMA + EtOH versus MDMA or EtOH alone. We next tested if reversible (tetrodotoxin, TTX) or permanent (6-hydrodoxyopamine, 6-OHDA) lesion of the VS could affect locomotor response to MDMA and MDMA + EtOH. Finally, we blocked dopamine D1 or glutamate NMDA receptors in the VS and measured the effects of MDMA and MDMA + EtOH on locomotor activity. We showed that bilateral reversible inactivation (TTX) or permanent lesion (6-OHDA) of the VS prevented the potentiation by EtOH of MDMA-induced locomotor hyperactivity. Likewise, blockade of D1 or NMDA receptors in the VS also reduced the potentiation of MDMA locomotor activity by EtOH. These data indicate that dopamine D1 and glutamate NMDA receptor-driven mechanisms in the VS play a key role in the pharmacodynamics of EtOH-induced potentiation of the locomotor effects of MDMA.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: N-Metil-3,4-Metilenodioxianfetamina / Etanol / Estriado Ventral Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: N-Metil-3,4-Metilenodioxianfetamina / Etanol / Estriado Ventral Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article