ANTIBODIES DIRECTED AGAINST ALPHA-SUBUNITS OF G(I), G(X Z), G(O) AND G(S) TRANSDUCER PROTEINS REDUCED THE MORPHINE-WITHDRAWAL SYNDROME IN MICE/

The effect of intracerebroventricular (i.c.v.) injection of antibodies directed against alpha subunits of G(i), G(x/z), G(O) and G(S) regula tory proteins on morphine dependence was analyzed in mice. Animals wer e rendered tolerant-dependent by subcutaneous (s.c.) implantation of a n oily suspension (10 ml/kg) containing 0.1 g/ml of morphine. After 72 h of chronic morphine, 1 mg/kg s.c. naloxone precipitated the withdra wal syndrome. The anti G(i2)alpha, G(x/z)alpha, G(O1/2)alpha and G(S) alpha antibodies given 24 h before starting the chronic morphine treat ment, reduced the number of jumps recorded. An effect also produced by pertussis toxin, agent impairing the function of G(i)/G(O) transducer proteins. The antibodies injected 24 h before the naloxone challenge reduced the number of animals presenting the jumping behavior, as well as the average number of jumps. This was observed for antibodies agai nst a subunits of G(i), G(x/z) and G(O1/2) proteins. Thus, i.c.v. inje ction of anti Get antibodies by reducing the function of opioid and no n-opioid receptors alleviated the morphine withdrawal syndrome.