Dependency on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine

Concomitant intracerebroventricular (i.c.v.) injection of anti-arginine vasopressin (AVP) antiserum dose-dependently suppressed the development of analgesic tolerance to daily morphine, 10 mg/kg, s.c., in mice. This suppressive effect of the antiserum was reduced by incubating the antiserum with AVP in vitro, before i.c.v. injection, suggesting that the antiserum inactivates brain AVP to result in the suppression of the development of morphine tolerance. Meanwhile, the administration of antiserum dose-dependently recovered respectively, suppressed the development of morphine tolerance. Meanwhile, the administration of antiserum dose-dependently recovered morphine analgesia in morphine-tolerant mice and a complete recovery of analgesia was observed at the highest dose of antiserum following the second injection, and the effect of antiserum was maintained for 3 days after its withdrawal. Likewise, 10–100 ng/mouse of AVP V 1 receptor antagonist given i.c.v. recovered morphine analgesia partially but significantly in a dose-dependent manner: however, AVP V 2 receptor antagonist at the same doses partially recovered analgesic effect but the effect was neither significant nor dose-dependent. These findings suggest that the tolerance developed to morphine can be reversible when disturbing the function of brain AVP, but in addition to the different mechanisms of antiserum, V 1 and V 2 receptor antagonists, the V 1 receptor-mediated mechanisms may be more closely concerned in this phenomenon.