DILTIAZEM INHIBITS NALOXONE-PRECIPITATED AND SPONTANEOUS MORPHINE-WITHDRAWAL IN RATS

The effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipit ated and spontaneous morphine withdrawal were studied in male Sprague- Dawley rats. In naloxone-precipitated withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by di ltiazem injected 4 or 2 and 4 h before naloxone, respectively. Three a dministrations of diltiazem (17, 11 and 5 h before naloxone) did not r educe the above withdrawal signs. Diarrhea was dose dependently inhibi ted by all schedule of diltiazem treatments. In spontaneous withdrawal , body weight loss and plasma corticosterone elevation were dose depen dently inhibited by two (6 and 12 h) or three (6, 12 and 18 h after th e last morphine) treatments with diltiazem at 6-h intervals after the last morphine, but not by a single diltiazem injected 18 h after the l ast morphine.