title: Withdrawal from cocaine self-administration and yoked cocaine delivery dysregulates glutamatergic mGlu5 and NMDA receptors in the rat brain.
abstract: In human addicts and in animal models, chronic cocaine use leads to numerous alterations in glutamatergic transmission, including its receptors. The present study focused on metabotropic glutamatergic receptors type 5 (mGluR(5)) and N-methyl-D-aspartate receptor subunits (NMDAR: GluN1, GluN2A, GluN2B) proteins during cocaine self-administration and after 10-day of extinction training in rats. To discriminate the contingent from the non-contingent cocaine delivery, we employed the "yoked"-triad control procedure. Protein expression in rat prefrontal cortex, nucleus accumbens, hippocampus, and dorsal striatum was determined. We also examined the Homer1b/c protein, a member of the postsynaptic density protein family that links NMDAR to mGluR(5). Our results revealed that cocaine self-administration selectively increased GluN1 and GluN2A subunit in the rat hippocampus and dorsal striatum, respectively, while mGluR(5) protein expression was similarly increased in the dorsal striatum of both experimental groups. Withdrawal from both contingent and non-contingent cocaine delivery induced parallel increases in prefrontal cortical GluN2A protein expression, hippocampal mGluR(5), and GluN1 protein expression as well as in accumbal GluN1 subunit expression, while the mGluR(5) expression was reduced in the prefrontal cortex. Extinction training in animals with a history of cocaine self-administration resulted in an elevation of the hippocampal GluN2A/GluN2B subunits and accumbal mGluR(5), and in a 50 % decrease of mGluR(5) protein expression in the dorsal striatum. The latter reduction was associated with Homer1b/1c protein level decrease. Our results showed that both contingent and non-contingent cocaine administration produces numerous, brain region specific, alterations in the mGluR(5), NMDA, and Homer1b/1c protein expression which are dependent on the modality of cocaine administration.
authors.affiliation: Department of Toxicology, Department of Biochemical Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Medyczna 9, 30-688, Kraków, Poland, lpomiern@cm-uj.krakow.pl.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Pomierny-Chamiolo
authors.forename: Joanna
authors.initials: J
authors.lastname: Miszkiel
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Frankowska
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pomierny
authors.forename: Ewa
authors.initials: E
authors.lastname: Niedzielska
authors.forename: Irena
authors.initials: I
authors.lastname: Smaga
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D005108:Extinction, Psychological / Q000187:drug effects; D000072233:Homer Scaffolding Proteins; D008297:Male; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C578937:Grm5 protein, rat; D000072233:Homer Scaffolding Proteins; D021122:Protein Subunits; D064529:Receptor, Metabotropic Glutamate 5; D016194:Receptors, N-Methyl-D-Aspartate; D003042:Cocaine