Effects of intracerebroventricular beta-funaltrexamine on mu and delta opioid receptors in the rat: dichotomy between binding and antinociception

Eur J Pharmacol. 1991 Oct 15;203(2):195-202. doi: 10.1016/0014-2999(91)90715-3.


The effects of intracerebroventricular (i.c.v.) beta-funaltrexamine (beta-FNA) pretreatment at -24 or -6 h were studied on mu and delta opioid receptor binding and on antinociception produced by i.c.v. morphine in rats. Mu and delta opioid receptor binding in brain membrane preparations was performed with [3H][D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) and [3H][D-Pen2,D-Pen5]enkephalin (DPDPE) as radiolabeled ligands, respectively. Effects of i.c.v. beta-FNA (24 h) on mu and delta binding depended on dosage. For [3H]DAGO binding, 3 micrograms beta-FNA did not affect either the Kd or Bmax, whereas 10 micrograms increased the Kd without changing the Bmax. beta-FNA pretreatment for 24 h did not alter [3H]DPDPE binding at 3 micrograms; at 10 micrograms, the Kd was increased with no change in the Bmax. Pretreatment with 10 micrograms beta-FNA for 6 h gave similar results to the 24-h treatment in mu binding, but did not change delta binding. When mu binding was performed on various brain regions, pretreatment with 10 micrograms beta-FNA for 24 h increased the Kd in all regions studied (the periaqueductal gray, thalamus, striatum and cortex). However, this pretreatment decreased the Bmax only in the periaqueductal gray (by 22%) and cortex (by 14%). Pretreatment of rats with beta-FNA (3 or 10 micrograms at -24 h), which by itself caused some hyperalgesia, greatly antagonized the antinociceptive effect of morphine (10 micrograms i.c.v.) in the hot-plate test. Our work with beta-FNA has revealed an apparent discrepancy between binding and behavioral results. This dichotomy may, in part, be the result of the limited distribution of beta-FNA to the periventricular area.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / metabolism
  • Injections, Intravenous
  • Kinetics
  • Male
  • Morphine / pharmacology
  • Naltrexone / analogs & derivatives*
  • Naltrexone / metabolism
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology*
  • Nociceptors / drug effects*
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Thalamus / drug effects
  • Thalamus / metabolism
  • Time Factors
  • Tritium


  • Enkephalins
  • Narcotic Antagonists
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Tritium
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Naltrexone
  • beta-funaltrexamine
  • Morphine
  • Enkephalin, D-Penicillamine (2,5)-