Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates

García-Pardo, María Pilar; Roger-Sánchez, C.; Rodrı́guez-Arias, Marta; Miñarro, José; Aguilar, M.A.

doi:10.1016/j.ejphar.2016.03.065

Cited by 38 publications

(28 citation statements)

References 199 publications

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“…One possibility is a change in the recruitment of scaffolding proteins associated with mGluR 5 such as Homer, Shank, and postsynaptic density protein-95, certain of which have been shown to be involved in cocaine-mediated behavior (Swanson et al, 2001; Wang et al, 2013; Bakshi et al, 2014; Martinez et al, 2014). The complexity of cocaine-induced changes to signaling transduction pathways and the validity of rodent models to develop new treatment strategies has recently been reviewed and highlights the importance of continuing our efforts in elucidating the molecular changes in signaling transduction in order to develop better drug targets for the treatment of cocaine addiction (Terbeck et al, 2015; Garcia-Pardo et al, 2016; Mihov and Hasler, 2016). …”

Section: Discussionmentioning

confidence: 99%

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Hoffmann

Crouzin

Moreno

et al. 2016

IJNPPY

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Background:Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise.Methods:We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission.Results:We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein. Interestingly, the group I metabotropic glutamate receptor antagonist/inverse-agonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride, led to a specific increase in cAMP responsive-element binding protein phosphorylation after chronic cocaine self-administration, specifically in the nucleus accumbens, but not in the striatum.Conclusions:Prolonged cocaine self-administration, through withdrawal, leads to a blunting of group I metabotropic glutamate receptor responses in the striatum. In addition, specifically in the accumbens, group I metabotropic glutamate receptor signaling to cAMP responsive-element binding protein shifts from an agonist-induced to an antagonist-induced cAMP responsive-element binding protein phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Hoffmann

Crouzin

Moreno

et al. 2016

IJNPPY

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“…Third, its inhibition in the brain leads to blockade of cocaine-mediated responses. Fourth, its implication in both memory consolidation and reconsolidation processes predicts a relevant adjuvant role in the definition of behavioural therapies to treat addiction (Fasano and Brambilla, 2011; Cerovic et al, 2013; Pascoli et al, 2014; Garcia-Pardo et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

“…In particular, Ras-ERK signalling has been implicated in both the acute and long-term effects of cocaine using different experimental paradigms that mimic drug addiction in humans (Valjent et al, 2000; Lu et al, 2005; Valjent et al, 2006a, 2006b; Lu et al, 2006; Ferguson et al, 2006; Girault et al, 2007; Fasano et al, 2009; Fasano and Brambilla, 2011; Pascoli et al, 2011, 2012, 2014; Cahill et al, 2014; Garcia-Pardo et al, 2016). The use of pharmacological inhibitors of MEK1/2, the kinases upstream of ERK1/2, has been essential in defining the role of ERK cascade in lasting experience- and drug-dependent alterations in behavioural plasticity.…”

Section: Introductionmentioning

confidence: 99%

Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

Papale

Morella

Indrigo

et al. 2016

eLife

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Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction.DOI: http://dx.doi.org/10.7554/eLife.17111.001

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“…Este campo de estudio es relativamente reciente a nivel mundial (Spear, 2007) y su historia en Colombia aún no ha sido descrita en detalle debido a la carencia de estudios en nuestro país relacionados con la temática. El uso de un amplio rango de modelos animales − desde especies de invertebrados a primates − ha jugado un papel importante en el desarrollo de esta área de investigación, en tanto ha permitido, entre otros, una mejor comprensión de la neurobiología del aprendizaje, la memoria, las emociones, la motivación, y la relación entre los anteriores procesos psicológicos y trastornos como la enfermedad de Alzheimer, esquizofrenia, ansiedad, depresión y adicciones (Flores, Morales-Medina & Diaz, 2016;Ganella & Kim, 2014;García-Pardo, Roger-Sanchez., Rodríguez-Arias, Miñarro & Aguilar, 2016;Morici, Bekinschtein & Weisstaub, 2015;Possin et al, 2016;Qiao et al, 2016). Así mismo, se ha avanzado en la comprensión tanto de algunas enfermedades del sistema nervioso como de posibles alternativas de tratamientos, y se han establecido relaciones entre genes, ambiente y comportamiento (Blaze, Asok & Roth, 2015;Homberg et al, 2016;Ortega & Rueda Pérez, 2011).…”

Section: Neurociencias Comportamentalesunclassified

Impacto y calidad de la productividad académica de los investigadores en Colombia en neurociencia comportamental utilizando modelos animales

et al. 2017

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La productividad científica colombiana es limitada considerando indicadores como el número de artículos publicados en revistas de alto impacto y el índice h. La ausencia de una línea de base y de metodologías de comparación de productividad dificulta trazar las expectativas de publicación provenientes de las instancias nacionales. El objetivo del presente estudio es el de evaluar de manera comparativa aspectos relacionados con el impacto y la calidad de la productividad académica de los investigadores en neurociencia comportamental utilizando modelos animales en Colombia. Se encontró que aunque los investigadores en Colombia publican de manera significativa (0.9 artículos por año), están rezagados en todos los aspectos de productividad con relación a investigadores internacionales. Se espera que la metodología propuesta pueda extenderse a la evaluación del impacto y calidad de la productividad en temáticas específicas de otras áreas de investigación.

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Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates

Cited by 38 publications

References 199 publications

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

Impacto y calidad de la productividad académica de los investigadores en Colombia en neurociencia comportamental utilizando modelos animales

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Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates

Cited by 38 publications

References 199 publications

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

Impacto y calidad de la productividad académica de los investigadores en Colombia en neurociencia comportamental utilizando modelos animales

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Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration