Effects of centrally administered naloxone on gastrointestinal myoelectrical activity in morphine-dependent rats

The gastrointestinal myoelectrical alterations associated with morphine tolerance and subsequent withdrawal with naloxone were studied before and after treatment with adrenergic blockers, atropine, indomethacin and methysergide administered either i.c.v. or s.c. The rats were prepared chronically with electrodes implanted on the stomach, duodeno-jejunum and colon and two small polyethylene catheters were inserted into the lateral ventricles of the brain. They were rendered physically dependent on morphine by the s.c. administration of a slow-release emulsion containing morphine (75 mg over 48 hr). Morphine treatment was associated with an immediate (15-30 min) inhibition of gastric and colonic spiking activity and intestinal migrating myoelectric complex lasting 6 to 8 hr, followed by a partial recovery of gastric spiking activity while a permanent disorganized motility pattern persisted on the intestine. After 48 hr of morphine treatment the i.c.v. and s.c. administrations of naloxone at doses of 0.03 and 3 mg X kg-1, respectively, promoted typical electrical activity lasting 2 to 3 hr, characterized by the presence of five to seven grouped spike bursts and termed "minute rhythm." Previous central but not peripheral administration of either tolazoline or phentolamine at a dose of 0.3 mg X kg-1 inhibited the i.c.v. naloxone precipitated withdrawal. Neither atropine i.c.v. (30 micrograms X kg-1) nor methysergide i.c.v. (20 micrograms X kg-1) and s.c. (0.2 mg X kg-1) nor indomethacin s.c. (4 mg X kg-1) were found to have any effect on i.c.v. naloxone induced minute rhythm pattern.(ABSTRACT TRUNCATED AT 250 WORDS)