Evidence map›Paper›PMID 25539508›Full record

ArticleThe international journal of neuropsychopharmacology2014

Cocaine-induced behavioral sensitization is associated with changes in the expression of endocannabinoid and glutamatergic signaling systems in the mouse prefrontal cortex.

Eduardo Blanco, Francisco J Pavón, Ana Palomino, María Jesús Luque-Rojas, Antonia Serrano, Patricia Rivera, Ainhoa Bilbao, Francisco Alen, Margarita Vida, Juan Suárez and 1 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.0field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 45 citations in OpenAlex.

  1. The acute effect of cannabis on plasma, liver and brain ammonia dynamics, a translational study.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2017
    Trial
  2. FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Eduardo BlancoUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Francisco J PavónUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Ana PalominoUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
María Jesús Luque-RojasUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Antonia SerranoUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Patricia RiveraUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Ainhoa BilbaoUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Francisco AlenUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Margarita VidaUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Juan SuárezUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao).
Fernando Rodríguez de FonsecaUnidad de Gestión Clínica de Salud Mental, Instituto IBIMA-Hospital Regional Universitario de Málaga, Málaga, Spain (Drs Blanco, Pavón, Palomino, Luque-Rojas, Serrano, Rivera, Alen, Vida, Suárez, and de Fonseca); Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain (Dr Blanco); Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany (Dr Bilbao). fernando.rodriguez@fundacionimabis.org.
Instituto de Investigación Biomédica de Málaga · ESHospital Regional Universitario de Málaga · ESUniversidad de Málaga · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndocannabinoids 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.

methodsWe 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.

resultsAlthough 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.

conclusionsThese 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.

Indexed as

AmidohydrolasesAnimalsCocaineDopamine Uptake InhibitorsDyskinesia, Drug-InducedEndocannabinoidsFatty Acid Amide HydrolasesGlutamic AcidGlutaminaseLipoprotein LipaseMaleMice, Inbred C57BLMonoacylglycerol LipasesPhospholipase DPrefrontal CortexReceptor, Cannabinoid, CB1AmidohydrolasesCocaineDopamine Uptake InhibitorsEndocannabinoidsFatty Acid Amide HydrolasesGlutamic AcidGlutaminaseLipoprotein LipaseMonoacylglycerol LipasesPhospholipase DReceptor, Cannabinoid, CB1Receptors, GlutamateRNA, Messengercannabinoidcocaineglutamateprefrontal cortex.sensitization

Identifiers

PMID25539508
PMCPMC4368868
OpenAlexW2181626027

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.