Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2227
Título : Cocaine-induced behavioral sensitization is associated with changes in the expression of endocannabinoid and glutamatergic signaling systems in the mouse prefrontal cortex.
Autor : Blanco, Eduardo
Pavón, Francisco J
Palomino, Ana
Luque-Rojas, María Jesús
Serrano, Antonia
Rivera, Patricia
Bilbao, Ainhoa
Alen, Francisco
Vida, Margarita
Suárez, Juan
Rodríguez de Fonseca, Fernando
Filiación: [Blanco,E; Pavón,FJ; Palomino,A; Luque-Rojas,MJ; Serrano,A; Rivera,P; Alen,F; Vida,M; Suárez,J; Rodríguez de Fonseca,F] Unidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain. [Blanco,E] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain. [Bilbao,A] Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
Palabras clave : Cannabinoid
Cocaine
Sensitization
Glutamate
Prefrontal cortex
Cocaína
Inhibidores de la captación de dopamina
Discinesia inducida por medicamentos
Corteza prefrontal
ARN mensajero
Receptor cannabinoide CB1
Receptores de glutamato
Dopamine Uptake Inhibitors
MeSH: Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aza Compounds::Azabicyclo Compounds::Tropanes::Cocaine
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Neurotransmitter Uptake Inhibitors::Dopamine Uptake Inhibitors
Medical Subject Headings::Diseases::Substance-Related Disorders::Poisoning::Drug Toxicity::Dyskinesia, Drug-Induced
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Acidic::Glutamic Acid
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::Glutaminase
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Lipoprotein Lipase
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Monoacylglycerol Lipases
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Frontal Lobe::Prefrontal Cortex
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Neurotransmitter::Receptors, Amino Acid::Receptors, Glutamate
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases
Fecha de publicación : 31-Jan-2015
Editorial : Oxford University Press
Cita Bibliográfica: Blanco E, Pavon FJ, Palomino A, Luque-Rojas MJ, Serrano A, Rivera P, et al. Cocaine-induced behavioral sensitization is associated with changes in the expression of endocannabinoid and glutamatergic signaling systems in the mouse prefrontal cortex. Int J Neuropsychopharmacol. 2014;18(1). pii: pyu024.
Abstract: BACKGROUND Endocannabinoids modulate the glutamatergic excitatory transmission by acting as retrograde messengers. A growing body of studies has reported that both signaling systems in the mesocorticolimbic neural circuitry are involved in the neurobiological mechanisms underlying drug addiction. METHODS We investigated whether the expression of both endocannabinoid and glutamatergic systems in the prefrontal cortex (PFC) were altered by an acute and/or repeated cocaine administration schedule that resulted in behavioral sensitization. We measured the protein and mRNA expression of the main endocannabinoid metabolic enzymes and the cannabinoid receptor type 1 (CB1). We also analyzed the mRNA expression of relevant components of the glutamate-signaling system, including glutamate-synthesizing enzymes, metabotropic receptors, and ionotropic receptors. RESULTS Although acute cocaine (10 mg/kg) produced no significant changes in the endocannabinoid-related proteins, repeated cocaine administration (20 mg/kg daily) induced a pronounced increase in the CB1 receptor expression. In addition, acute cocaine administration (10 mg/kg) in cocaine-sensitized mice (referred to as cocaine priming) induced a selective increase in the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). These protein changes were accompanied by an overall decrease in the ratios of endocannabinoid synthesis/degradation, especially the N-acyl phosphatidylethanolamine phospholipase D/FAAH and diacylglycerol lipase alpha/MAGL ratios. Regarding mRNA expression, while acute cocaine administration produced a decrease in CB1 receptors and N-acyl phosphatidylethanolamine phospholipase D, repeated cocaine treatment enhanced CB1 receptor expression. Cocaine-sensitized mice that were administered priming injections of cocaine mainly displayed an increased FAAH expression. These endocannabinoid changes were associated with modifications in glutamatergic transmission-related genes. An overall decrease was observed in the mRNA expression of the glutamate-synthesizing gene kidney-type glutaminase (KGA), the metabotropic glutamate receptors (mGluR3 and GluR), and subunits of NMDA ionotropic receptors (NR1, NR2A, NR2B and NR2C) after acute cocaine administration, while mice repeatedly exposed to cocaine only displayed an increase in NR2C. However, in cocaine-sensitized mice primed with cocaine, this inhibition was reversed and a strong increase was detected in the mGluR5, NR2 subunits, and both GluR1 and GluR3. CONCLUSIONS These findings indicate that cocaine sensitization is associated with an endocannabinoid downregulation and a hyperglutamatergic state in the PFC that, overall, contribute to an enhanced glutamatergic input into PFC-projecting areas.
Descripción : Journal Article; Research Support, Non-U.S. Gov't;
URI: http://hdl.handle.net/10668/2227
Versión del editor : http://ijnp.oxfordjournals.org/content/18/1/pyu024.long
DOI: 10.1093/ijnp/pyu024
ISSN : 1469-5111 (Online)
1461-1457 (Print)
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

Files in This Item:
File Description SizeFormat 
BlancoE_CocaineInducedBehavioral.pdfArtículo publicado1,05 MBAdobe PDFView/Open
BlancoE_CocaineInduced_Tables_AJE8.docxTablas19,43 kBMicrosoft Word XMLView/Open


This item is licensed under a Creative Commons License Creative Commons