A lack of supersensitivity to opioid receptor agonists following chronic spinal opioid receptor antagonist administration in the rat.

A lack of supersensitivity to opioid receptor agonists following chronic spinal opioid receptor antagonist administration in the rat.

Keck B J; Stafinsky J L; Uram M; Crisp T

General pharmacology

1995

1995-01

1. Male Sprague-Dawley rats were chronically tested with intrathecal (i.t.) receptor selective opioid antagonists to determine if antinociceptive supersensitivity developed to selective i.t. opioid receptor agonists. 2. A subcutaneously implanted osmotic minipump was used to deliver the mu-opioid receptor antagonist CTOP (0.3 nmol) or the delta-opioid receptor antagonist naltrindole (5.5 nmol) for 7 days. 3. Following a 24 hr washout period, rats received a single i.t. dose (ED50) of either DAMPGO (for CTOP-treated animals) or DPDPE (for naltrindole-treated animals) and the antinociceptive effects of the agents were tested on the tail-flick test. 4. Our findings revealed that chronic spinal treatment with selective opioid receptor antagonists did not induce an antinociceptive supersensitivity to selective opioid receptor agonists. 5. Perhaps this lack of supersensitivity is reflective of difficulties inherent to opioid receptor antagonists that do not possess negative intrinsic activity.

5)-; Ala(2)-MePhe(4)-Gly(5)-; Animals; D-Penicillamine (2; Dose-Response Relationship; Drug; Enkephalin; Enkephalins/*pharmacology; Male; Naltrexone/analogs & derivatives/pharmacology; Narcotic Antagonists/*pharmacology; Opioid/*drug effects; Rats; Receptors; Somatostatin/analogs & derivatives/pharmacology; Species Specificity; Spinal Cord/*drug effects; Sprague-Dawley

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