Reduced ethanol response in the alcohol-preferring RHA rats and neuropeptide mRNAs in relevant structures.
Roman rat strains, genetically selected for high (RHA) or low (RLA) active avoidance acquisition in the two-way shuttle box, differ in dopaminergic activity. These two strains appear to be a valid laboratory model of divergent sensation/novelty and substance-seeking profiles. RHA rats show higher ethanol intake and preference than do RLA rats, and it was suggested that RHA rats are more tolerant than RLA to the effects of alcohol. In the hole-board test, we found that the non-alcohol-preferring RLA rats showed enhanced responsiveness to the stimulatory effects of intraperitoneal administration of 0.25 g/kg ethanol when compared with RHA rats. In situ hybridization analysis showed higher levels of preprodynorphin in the accumbens shell and higher levels of preproenkephalin in the cingulate cortex in RHA rats. RLA rats showed higher levels of enkephalin gene transcripts in restricted areas of the dorsal striatum. Finally, differences in cholecystokinin gene transcript, suggestive of a different arrangement of certain interneurons, were found in different cortical areas. The differences in peptide gene expression found between the two strains might reflect the differences in alcohol preference and sensitivity. RHA rats may have more predictive value than other rodent alcoholism models, as high initial tolerance to ethanol is a risk factor for alcoholism in humans.
Guitart-Masip
Marc
M
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Neuroscience Institute, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Giménez-Llort
Lydia
L
Fernández-Teruel
Albert
A
Cañete
Toni
T
Tobeña
Adolf
A
Ogren
Sven Ove
SO
Terenius
Lars
L
Johansson
Björn
B
D000428:Alcohol Drinking / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002492:Central Nervous System Depressants; D004745:Enkephalins; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; C036448:pre-prodynorphin; D000431:Ethanol; D004399:Dynorphins; D002766:Cholecystokinin