Inhibition of the brain to blood transport system for enkephalins and Tyr-MIF-1 in mice addicted or genetically predisposed to drinking ethanol.
Enkephalin concentrations in the brain correlate inversely with ethanol intake and the predisposition of different strains of mice to drink. This and other evidence link ethanol ingestion, addiction, and withdrawal to opiate peptides. We studied the effect of these conditions on the saturable, stereospecific system that transports the enkephalins and Tyr-MIF-1 (a peptide with antiopiate action) out of the brain. The transport rate in mice physically dependent on ethanol was only 56% of the rate in control mice, but during withdrawal from ethanol transport rates increased to levels seen in controls. Transport rates were also lower in strains of mice previously determined to have lower enkephalin concentrations in the brain and to be predisposed to drinking ethanol. Acute intraperitoneal or intracerebroventricular injection of ethanol had minimal direct effects on the transport rate, suggesting that it is not ethanol itself, but those factors associated with addiction and the predisposition to drink ethanol, that altered transport. These studies raise the possibility that the inhibition of this system that transports enkephalins/Tyr-MIF-1 out of the brain might offer a new approach to the control of drinking and withdrawal from ethanol.
Banks
W A
WA
Veterans Administration Medical Center, New Orleans, LA.
Kastin
A J
AJ
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004745:Enkephalins / Q000097:blood / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D013045:Species Specificity
D004745:Enkephalins; D000431:Ethanol; C036930:tyrosyl-prolyl-leucyl-glycinamide; D009075:MSH Release-Inhibiting Hormone