ANTIBODIES DIRECTED AGAINST THE MU-OPIOID RECEPTOR ALLEVIATED MULTIPLE SIGNS OF MORPHINE-WITHDRAWAL IN MICE

An investigation was made into the effect of intracerebroventricular ( i.c.v.) administration of antibodies to the amino-terminal portion 1-1 6 (MDSSTGPGNTSDCSDP) or the peptide sequence 208-216 (TKYRQGSID) of th e cloned mu-opioid receptor (mu-OR) on morphine tolerance and dependen ce. Animals were rendered tolerant-dependent by subcutaneous (s.c.) im plantation of an oily morphine suspension. To precipitate withdrawal s yndrome, the opioid antagonist naloxone (1 mg/kg, s.c.) was administer ed 72 h after chronic morphine treatment. In mice i.c.v. injected with the anti-mu-OR antibodies, the analgesic effect of chronic morphine w as significantly reduced. These antibodies given 24 h before starting the chronic morphine treatment, reduced most of the symptoms associate d with the withdrawal syndrome (jumps, loss of body weight, diarrhoea and body shakes) elicited by naloxone in dependent mice. The administr ation of the antisera to mice undergoing 48 h of chronic morphine trea tment did not precipitate detectable signs of abstinence, but reduced the withdrawal syndrome precipitated by naloxone 24 h later. The findi ng that both antibodies impaired mu(1)/mu(2)-mediated effects, suggest s a high degree of homology between the pharmacologically defined subt ypes of mu-OR.