The neuronal mechanisms underlying the development of opioid tolerance and dependence have eluded researchers for decades. Recent investigations of a novel pharmacological class of compounds, called neutral antagonists, indicate that these compounds may attenuate effects produced by agonists but fail to produce effects of their own. In addition, neutral antagonists appear to reverse the effects produced by traditional antagonists in vivo and in vitro. A class of somatostatin analogues has been synthesized that includes selective high-affinity opioid ligands that may be candidates as neutral antagonists for the mu-opioid receptor. A few current reports have indicated that these purported neutral antagonists reverse opiate withdrawal produced by traditional mu-opiate receptor antagonists. The goal of the proposed experiments is to evaluate the behavioral and pharmacological properties of the putative neutral antagonists in nondependent and morphine-dependent rats using a variety of analgesia and drug discrimination procedures. By providing the first systematic evaluation of the behavioral effects of neutral antagonists, these studies could radically alter the manner in which we think about opioid receptor pharmacology. Furthermore, because these drugs block the effects of mu opioids, but do not precipitate withdrawal, the findings of these experiments will be highly relevant to the treatment of opioid dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DA010776-05
Application #
6175466
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Schnur, Paul
Project Start
1997-09-01
Project End
2002-06-30
Budget Start
2000-07-13
Budget End
2001-06-30
Support Year
5
Fiscal Year
2000
Total Cost
$97,376
Indirect Cost
Name
Albert Einstein Medical Center (Philadelphia)
Department
Type
DUNS #
148406911
City
Philadelphia
State
PA
Country
United States
Zip Code
19141