CCK(B) receptor antagonist L365,260 potentiates the efficacy to and reverses chronic tolerance to electroacupuncture-induced analgesia in mice

Cholecystokinin octapeptide (CCK-8) is a physiological antagonist of endogenous opioids in the central nervous system (CNS). Our previous work has shown that CCK-8 plays an important role in the development of tolerance to morphine analgesia and electroacupuncture (EA) analgesia in the rat. The present studies were designed to examine whether the CCK(B) receptor is involved in the modulation of EA analgesia and the development of EA tolerance in mice. The latency to flick the tail in the radiant heat was used as index to assess the efficacy of EA analgesia. Subcutaneous (s.c.) injection of the CCK(B) receptor antagonist L365,260 produced a dose-dependent (0.125-2.0 mg/kg) potentiation of the analgesia induced by 100 Hz EA, with a maximal effect occurred at 0.5 mg/kg. In addition, L365,260 (0.5 mg/kg) significantly reversed chronic tolerance to 100 Hz EA in mice. These results suggest that the CCK(B) receptor might play a role in the tonic inhibition of 100 Hz EA-induced analgesia and in the mediation of chronic tolerance to 100 Hz EA in mice. The results opened a way for further investigation of the function of CCK-8 in pain modulation using inbred strains of mice.