The blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier are composed of specialized capillaries and astrocytic endfeet that serve to regulate the environment of the central nervous system. Peptide transport system-1 (PTS-1) is located at the BBB and transports the tetrapeptide methionine enkephalin (Met-enkephalin) from brain to blood. PTS-1 and transcription play important roles in the regulation of Met-enkephalin in vivo Met-enkephalin has been associated with the consumption of ethanol. Increasing concentrations of Met-enkephalin within the brain, either by delivering the peptide into the ventricular system or by inhibiting its degradation, reduces drinking. Opiate antagonists reduce the consumption of ethanol in laboratory animals and in humans In this work, the relationships among Met-enkephalin, PPE mRNA, and PTS-1 were studied in animal models of alcoholism. In outbred ICR mice, the consumption of ethanol results in an increase in concentrations of Met-enkephalin in whole brain. This increase correlates with a decrease in the transport of Met-enkephalin out of the brain by PTS-1. The activity of PTS-1 recovers quickly after the removal of ethanol, although it remains resistant to inhibition by serotonergic agents. Levels of PPE mRNA correlate with concentrations of Met-enkephalin in naive, but not exposed, mice. These results suggests that ethanol does not regulate concentrations of Met-enkephalin through a direct effect on transcription Withdrawal-seizure prone (WSP) and withdrawal-seizure resistant (WSR) mice serve as a genetic model for sensitivity to the effects of ethanol. In naive animals, concentrations of Met-enkephalin are greater in WSP mice than in WSR mice. This difference cannot be explained by differences in levels of PPE mRNA or in activity of PTS-1. After exposure to ethanol, the concentration of Met-enkephalin increased in WSR mice, reducing the gap between WSP and WSR mice. These change were not associated with changes in PPE mRNA or in the activity of PTS-1. Differences in the function of PTS-1 exist between WSP and WSR mice since concentrations of Met-enkephalin correlate with transport rates in WSR, but not in WSP, mice. The elevated baseline in concentrations of Met-enkephalin in WSP mice, coupled with the absence of an increase during withdrawal, suggests that WSP mice experience a novel form of enkephalin resistance / acase@tulane.edu
Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_25013 |
Date | January 1998 |
Contributors | Plotkin, Scott Randall (Author), Weber, Joseph T (Thesis advisor) |
Publisher | Tulane University |
Source Sets | Tulane University |
Language | English |
Detected Language | English |
Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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