Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain.
Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.
Lindholm
S
S
Clinical Alcohol and Drug Addiction Research, Department of Clinical Neuroscience, Magnus Huss, M4:02, Karolinska Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden. sara.lindholm@fyfa.ki.se
Ploj
K
K
Franck
J
J
Nylander
I
I
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry; D004399:Dynorphins / Q000032:analysis / Q000378:metabolism*; D004723:Endorphins / Q000032:analysis / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004723:Endorphins; D000431:Ethanol; D004744:Enkephalin, Methionine; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D004399:Dynorphins; C036200:rimorphin