title: Regulation of the immediate-early genes arc and zif268 in a mouse operant model of cocaine seeking reinstatement.
abstract: Reinstatement of extinguished operant responding for drug is an appropriate model of relapse to drug abuse. Due to the difficulty of implementing in mice the procedure of instrumental intravenous self-administration, mechanisms of reinstatement have so far been studied almost exclusively in rats. A mouse model of reinstatement of cocaine seeking has recently been characterized (Soria et al. 2008). The aim of the present study was to assess regional brain activation, as measured by induction of the immediate early genes (IEG) arc and zif268, during priming- or cue-elicited reinstatement of cocaine seeking using this new mouse model and the in situ hybridization technique. We have demonstrated that cue-elicited reinstatement of cocaine seeking was associated with induction of the IEG in the medial prefrontal cortex (prelimbic and infralimbic) and basolateral amygdala. Priming-induced reinstatement produced a more widespread up-regulation of those genes in forebrain regions including medial prefrontal, orbitofrontal and motor cortex, dorsal striatum and basolateral amygdala. These patterns of IEG expression are in agreement with previous results obtained in rats and thus indicate that the new mouse model of reinstatement is functionally equivalent to rat models. That comparability adds to the usefulness of the mouse model as a tool for addressing neurobiological mechanisms of addiction.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziółkowska
authors.forename: Michał
authors.initials: M
authors.lastname: Kiełbiński
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gieryk
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Soria
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewłocki
mesh_terms: D000818:Animals; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein