title: Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.
abstract: Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5 g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.
authors.affiliation: Department of Pharmacology, University of Bologna, Via Irnerio 48, Bologna, Italy. claudio.daddario@unibo.it
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Addario
authors.forename: Francesca F
authors.initials: FF
authors.lastname: Caputi
authors.forename: Roberto
authors.initials: R
authors.lastname: Rimondini
authors.forename: Ottavio
authors.initials: O
authors.lastname: Gandolfi
authors.forename: Elia
authors.initials: E
authors.lastname: Del Borrello
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism; D000435:Alcoholic Intoxication / Q000235:genetics / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000235:genetics* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression; D008297:Male; D018847:Opioid Peptides / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D057897:Reflex, Righting / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D000097629:Nociceptin
chemical_list: D002492:Central Nervous System Depressants; D004399:Dynorphins; D004745:Enkephalins; D000431:Ethanol; D018847:Opioid Peptides; D011498:Protein Precursors; D000097629:Nociceptin; C033660:preproenkephalin