Antibodies directed against α subunits of G i, G x/z, G o and G S transducer proteins reduced the morphine withdrawal syndrome in mice

Abstract

The effect of intracerebroventricular (i.c.v.) injection of antibodies directed against α subunits of G i, G x/z, G o and G s regulatory proteins on morphine dependence was analyzed in mice. Animals were rendered tolerant-dependent by subcutaneous (s.c.) implantation of an 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 withdrawal syndrone. The anti G i2α, G x/zα, G o 1 2 α and G sα antibodies given 24 h before starting the chronic morphine treatment, 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 against α subunits of G i, G x/z and G o 1 2 proteins. Thus, i.c.v. injection of anti Gα antibodies by reducing the function of opioid and non-opioid receptors alleviated the morphine withdrawal syndrome.