Distribution of the mu and delta opioid binding sites in the brain of the alcohol-preferring AA and alcohol-avoiding ANA lines of rats.
There is experimental evidence indicating that the positive reinforcing effects of ethanol, responsible for voluntary ethanol consumption, are in part mediated by the endogenous opioid system. Differences in some components of the endogenous opioid system have been observed between lines and strains of animals bred selectively for their high or low ethanol consumption. Our objective was to investigate the presence of differences in the density and distribution of mu and delta opioid receptors in the brain of the alcohol-preferring Alko-Alcohol and alcohol-avoiding Alko, NonAlcohol lines of rats using iodinated ligands specific for mu ([D-Ala2, MePhe4, Met(o)ol5]-Enkephalin (FK 33-824)) or for delta ([D-Ser2]-leucine enkephalin-Thr) opioid receptors. Results calculated from studies on membrane preparations of whole brain minus cerebellum indicated that the Bmax and Kd were similar between the two lines of rats; however, autoradiographic studies showed that the alko-alcohol rats presented significantly higher density of mu opioid receptors in some brain regions, including nuclei of the limbic system that are important in mediating the reinforcing properties of many drugs of abuse. Furthermore, studies on brain membrane preparations indicated that both lines of rats were deficient in high affinity delta binding sites compared to Sprague-Dawley rats. Indeed, autoradiographic studies confirmed the presence of low density of the high affinity binding sites for [D-Ser2]-leucine enkephalin-Thr in both lines of rats. However, the density of the high affinity delta binding sites was higher in some distinct brain regions of the Alko-Alcohol than Alko-NonAlcohol rats. These differences in the density of both mu and delta opioid receptors may be partially responsible for the differences in voluntary ethanol consumption exhibited by these two lines of rats.
de Waele
J P
JP
Douglas Hospital Research Center, McGill University, Montréal, Québec, Canada.
Kiianmaa
K
K
Gianoulakis
C
C
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000648:ultrastructure*; D002531:Cerebellum / Q000648:ultrastructure; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000032:analysis*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000032:analysis*
D000700:Analgesics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-