Decrease in δ-opioid receptor density in rat brain after chronic [d-Ala2,d-Leu5]enkephalin treatment

Pao Luh Tao, Li Ren Chang, Ping-Yee Law, Horace H Loh

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Chronic treatment of Sprague-Dawley rats with [d-Ala2,d-Leu5]enkephalin (DADLE) resulted in the development of tolerance to the antinociceptive effect of this opioid peptide. When opioid receptor binding was measured, time-dependent decreases in [3H]diprenorphine binding to the P2 membranes prepared from the cortex, midbrain and striatum were observed. Scatchard analysis of the saturation binding data revealed a decrease in Bmax values and no change in the Kd values of [3H]diprenorphine binding to these brain regions, indicative of down-regulation of the receptor. This reduction in the opioid receptor binding activities could be demonstrated to be due to the DADLE effect on the δ-opioid receptors in these brain regions. When [3H]DADLE binding was carried out in the presence of morphiceptin, a significant reduction in the δ-opioid receptor binding was observed in all brain areas tested. μ-Opioid receptor binding decrease was observed only in the striatum after 5 days of DADLE treatment. Additionally, the onset of δ-opioid receptor decrease in the midbrain area was rapid, within 6 h of the initiation of the chronic DADLE treatment. Thus, analogous to previous observations in which chronic etorphine treatment preferentially reduced μ-opioid receptor binding, chronic DADLE treatment preferentially reduced δ-opioid receptor binding activity.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalBrain Research
Issue number2
StatePublished - Oct 18 1988

Bibliographical note

Funding Information:
The present studies were supported in part by NIDA Grant DA-00564 and Grant NSC 75-0412-B016-07 from the National Science Council, Republic of China. H.H.L. is a recipient of National Institute of Drug Abuse Career Award K-02-DA-70554.

Copyright 2014 Elsevier B.V., All rights reserved.


  • Brain opioid receptor
  • Receptor
  • [d-Ala,d-Leu]enkephalin
  • δ-opioid


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