Propofol potentiates the depressant effect of alfentanil in isolated neonatal rat spinal cord and blocks naloxone-precipitated hyperresponsiveness.
Our previous studies have shown that a benzodiazepine potentiates opioid actions on spinal cord by blocking a hyperresponsiveness that may be related to the development of opioid tolerance and withdrawal. The present study was designed to test whether propofol, which like benzodiazepines acts on GABA(A) receptors, displays similar interactions with opioids. Spinal cords isolated from 1-7 day old rats were arranged to record the slow ventral root potential (sVRP) elicited by stimulating a lumbar dorsal root. A concentration of propofol which by itself did not depress sVRP significantly enhanced the apparent potency of alfentanil and blocked the increase in sVRP observed when alfentanil is followed by naloxone. The results suggest that enhancement of GABA inhibition may increase opioid potency by inhibiting the development of acute tolerance.
Feng
J Q
JQ
Department of Anesthesia, Stanford University School of Medicine, CA 94305-5117, USA.
Kendig
J J
JJ
D015760:Alfentanil / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D003864:Depression, Chemical; D004357:Drug Synergism; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D018756:GABA Antagonists; D009292:Narcotic Antagonists; D015760:Alfentanil; D009270:Naloxone; D001640:Bicuculline; D015742:Propofol