title: Repeated nicotine exposure modulates prodynorphin and pronociceptin levels in the reward pathway.
abstract: Nicotine dependence is maintained by neurobiological adaptations in the dopaminergic brain reward pathway with the contribution of opioidergic circuits. This study assessed the role of opioid peptides and receptors on the molecular changes associated with nicotine dependence. To this aim we analysed nicotine effects on opioid gene and receptor expression in the reward pathway in a nicotine sensitization model.
  
  
  
  Sprague-Dawley rats received nicotine administrations for five days and locomotor activity assessment showed the development of sensitization. The mRNA expression of prodynorphin (pdyn), pronociceptin (pnoc) and the respective receptors was measured by quantitative PCR in the ventral midbrain (VM), the nucleus accumbens (NAc), the caudate-putamen (CPu), the pre-frontal cortex (PFCx), and the hippocampus.
  
  
  
  A significant positive effect of sensitization on pdyn mRNA levels was detected in the CPu. This effect was supported by a significant and selective correlation between the two parameters in this region. Moreover, chronic but not acute nicotine treatment significantly decreased pdyn mRNA levels in the NAc and increased expression in the PFCx. Pnoc mRNA was significantly increased in the VM and the PFCx after sub-chronic administration of nicotine, whereas no alterations were observed after acute treatment. No treatment associated changes were detected in κ-opioid receptor or nociceptin receptor mRNAs.
  
  
  
  This experiment revealed an effect of nicotine administration that was distinguishable from the effect of nicotine sensitization. While several pnoc and pdyn changes were associated to nicotine administration, the only significant effect of sensitization was a significant increase in pdyn in the CPu.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy. Electronic address: lucia.carboni4@unibo.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: Carboni
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Romoli
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zoli
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D009042:Motivation / Q000187:drug effects* / Q000235:genetics*; D009043:Motor Activity / Q000187:drug effects; D009415:Nerve Net / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D018847:Opioid Peptides / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics; D012201:Reward; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000378:metabolism; D000094942:Nociceptin Receptor
chemical_list: D004298:Dopamine; D004745:Enkephalins; D009538:Nicotine; D018847:Opioid Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D000094942:Nociceptin Receptor; C119224:pronociceptin; C033660:preproenkephalin; C000722285:Oprl1 protein, rat
keywords: Dynorphin; Gene expression; Kappa opioid receptor; Nicotine sensitization; Nociceptin receptor; Orphanin FQ/nociceptin