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Adaptive Changes in Group 2 Metabotropic Glutamate Receptors Underlie the Deficit in Recognition Memory Induced by Methamphetamine in Mice.
Busceti, Carla Letizia; Di Menna, Luisa; Castaldi, Sonia; D'Errico, Giovanna; Taddeucci, Alice; Bruno, Valeria; Fornai, Francesco; Pittaluga, Anna; Battaglia, Giuseppe; Nicoletti, Ferdinando.
Afiliación
  • Busceti CL; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli 86077, Italy.
  • Di Menna L; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli 86077, Italy.
  • Castaldi S; Department of Physiology and Pharmacology, University Sapienza, Roma 00185, Italy.
  • D'Errico G; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli 86077, Italy.
  • Taddeucci A; Department of Pharmacy, University of Genova, Genova 16148, Italy.
  • Bruno V; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli 86077, Italy.
  • Fornai F; Department of Physiology and Pharmacology, University Sapienza, Roma 00185, Italy.
  • Pittaluga A; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli 86077, Italy.
  • Battaglia G; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56126, Italy.
  • Nicoletti F; Department of Pharmacy, University of Genova, Genova 16148, Italy.
eNeuro ; 11(8)2024 Aug.
Article en En | MEDLINE | ID: mdl-38969501
ABSTRACT
Cognitive dysfunction is associated with methamphetamine use disorder (MUD). Here, we used genetic and pharmacological approaches to examine the involvement of either Group 2 metabotropic glutamate (mGlu2) or mGlu3 receptors in memory deficit induced by methamphetamine in mice. Methamphetamine treatment (1 mg/kg, i.p., once a day for 5 d followed by 7 d of withdrawal) caused an impaired performance in the novel object recognition test in wild-type mice, but not in mGlu2-/- or mGlu3-/- mice. Memory deficit in wild-type mice challenged with methamphetamine was corrected by systemic treatment with selectively negative allosteric modulators of mGlu2 or mGlu3 receptors (compounds VU6001966 and VU0650786, respectively). Methamphetamine treatment in wild-type mice caused large increases in levels of mGlu2/3 receptors, the Type 3 activator of G-protein signaling (AGS3), Rab3A, and the vesicular glutamate transporter, vGlut1, in the prefrontal cortex (PFC). Methamphetamine did not alter mGlu2/3-mediated inhibition of cAMP formation but abolished the ability of postsynaptic mGlu3 receptors to boost mGlu5 receptor-mediated inositol phospholipid hydrolysis in PFC slices. Remarkably, activation of presynaptic mGlu2/3 receptors did not inhibit but rather amplified depolarization-induced [3H]-D-aspartate release in synaptosomes prepared from the PFC of methamphetamine-treated mice. These findings demonstrate that exposure to methamphetamine causes changes in the expression and function of mGlu2 and mGlu3 receptors, which might alter excitatory synaptic transmission in the PFC and raise the attractive possibility that selective inhibitors of mGlu2 or mGlu3 receptors (or both) may be used to improve cognitive dysfunction in individuals affected by MUD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Glutamato Metabotrópico / Ratones Noqueados / Reconocimiento en Psicología / Estimulantes del Sistema Nervioso Central / Metanfetamina / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: ENeuro Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Glutamato Metabotrópico / Ratones Noqueados / Reconocimiento en Psicología / Estimulantes del Sistema Nervioso Central / Metanfetamina / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: ENeuro Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos