The effect of ethanol drinking on opioid analgesia and receptors in mice.
Recent studies suggest substantial interactions between opioids and ethanol (EtOH). Both in vivo and in vitro experiments indicate that EtOH can regulate opioid systems and that opioids can modify EtOH consumption. In the present studies, we examined if EtOH consumption altered opioid receptors and the potency of opioid analgesics. Mice were given unlimited access to 6-7% EtOH alone for 7 days or were allowed to drink increasing concentrations (3-6%) of EtOH over 13-14 days. Controls had access to water. The EtOH groups drank significantly less volume than controls, although there were no significant differences in body weight or baseline nociception. The analgesic (tail flick) potency of SC morphine was decreased by approximately 1.6-2.0-fold in EtOH-treated mice. A single acute dose of EtOH (1 g/kg) that produced blood alcohol levels in excess of that for 7 day exposure to EtOH, did not change morphine's analgesic ED50, suggesting that chronic exposure to EtOH was necessary for the reduction in potency. The change in morphine potency was not due to pharmacokinetic differences because EtOH consumption did not modify the concentration of morphine in brain and spinal cord. The analgesic potency of a delta-opioid receptor agonist (ICV DSLET) was also decreased by approximately 2-fold. Saturation binding studies indicated no changes in the density or affinity of brain and spinal cord delta-opioid ([3H]DPDPE, [3H]DSLET, [3H]DeltorphinII) and mu-opioid ([3H]DAMGO) receptors. Similarly, there was no significant effect of EtOH on delta-opioid receptor mRNA in either brain or spinal cord preparations. Taken together, these data suggest that EtOH consumption decreases the analgesic potency of opioids in mice through a mechanism that is unrelated to pharmacokinetics or opioid receptor changes in brain and cord.
Shah
S
S
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439, USA.
Duttaroy
A
A
Sehba
F
F
Chen
B
B
Philippe
J
J
Monderson
T
T
Lau-Cam
C
C
Carroll
J
J
Yoburn
B C
BC
D000428:Alcohol Drinking / Q000503:physiopathology*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000493:pharmacokinetics / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011957:Receptors, Opioid / Q000819:agonists / Q000096:biosynthesis / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000096:biosynthesis; D013116:Spinal Cord / Q000378:metabolism
D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D000431:Ethanol; D009020:Morphine