visitant ::
identificació
|
|||||||||||||||
Cerca | Lliura | Ajuda | Servei de Biblioteques | Sobre el DDD | Català English Español |
Pàgina inicial > Articles > Articles publicats > Long-lasting impairment of mGluR5-activated intracellular pathways in the striatum after withdrawal of cocaine self-administration |
Data: | 2017 |
Resum: | 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 mGluR 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. |
Ajuts: | Ministerio de Educación y Ciencia SAF2006-08240 Ministerio de Ciencia e Innovación SAF2009-12510 Ministerio de Economía y Competitividad SAF2014-58396 Ministerio de Sanidad y Consumo RD06/0001/0015 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014SGR-1236 |
Nota: | ANECA |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Extracellular signal-regulated protein kinase1 and 2 ; Camp response element binding protein ; Cocaine self-administration withdrawal ; Striatum ; Long term depression |
Publicat a: | International journal of neuropsychopharmacology, Vol. 20 Núm. 1 (2017) , p. 72-82, ISSN 1469-5111 |
11 p, 1.7 MB |