title: Alteration of kappa-opioid receptor system expression in distinct brain regions of a genetic model of enhanced ethanol withdrawal severity.
abstract: Abrupt withdrawal from chronic alcohol exposure can produce convulsions that are likely due to ethanol (EtOH) neuroadaptations. While significant efforts have focused on elucidating dependence mechanisms, the alterations contributing to EtOH withdrawal severity are less well characterized. The present studies examined the kappa-opioid receptor (KOP-R) system in Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice, selected lines that display severe and mild convulsions upon removal from chronic EtOH exposure. Previous data demonstrated significant increases in whole brain prodynorphin (Pdyn) mRNA in WSP mice only during EtOH withdrawal. No significant effects of EtOH exposure or withdrawal were observed in WSR mice. The present study characterized Pdyn mRNA and the KOP-R in WSP and WSR mice during EtOH withdrawal using in situ hybridization (ISH) and KOP-R autoradiography. Analyses were performed in brain regions that express Pdyn mRNA and/or KOP-R and that might participate in seizure circuitry: the piriform cortex, olfactory tubercle, nucleus accumbens, caudate-putamen, claustrum, dorsal endopiriform nucleus, and cingulate cortex. ISH analyses confirmed previous findings; EtOH withdrawal increased Pdyn mRNA in multiple brain regions of WSP mice, but not WSR. Basal KOP-R binding was higher in WSR mice than in WSP mice, suggesting an anti-convulsant role for receptor activation. Finally, increased KOP-R density was present during EtOH withdrawal in WSP mice. These data suggest that differences in the KOP-R system among the lines might contribute to their selected difference in EtOH withdrawal severity.
authors.affiliation: Neuroscience Graduate Program, Oregon Health & Science University, Portland, 97239, USA. bohlinga@ohsu.edu
authors.forename: Amy S
authors.initials: AS
authors.lastname: Beadles-Bohling
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Wiren
mesh_terms: D020270:Alcohol Withdrawal Seizures / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D002492:Central Nervous System Depressants; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D000431:Ethanol; C033660:preproenkephalin