Potentiation of Electroacupuncture-Induced Analgesia by Cck-B Antagonist L-365, 260 in Wistar Rats but Not in Acoustically-Evoked Epileptic Rats

Abstract

Cholecystokinin octapeptide (CCK-8) is a neuropeptide with potent anti-opioid activity, which can antagonize morphine analgesia at nanogram dosage through activation of the CCK-B receptor in the central nervous system (CNS) of the rat. In the present study the CCK-B antagonist L-365,260 was injected intracerebroventricularly (icv) to Wistar rats to see its effect on the analgesia induced by electroacupuncture (EA) stimulation. A marked potentiation of EA-induced analgesia was observed. This potentiation was more prominent when EA of higher frequency was used, showing a rank order of 100Hz > 15Hz = 2/15Hz ≫ 2Hz. In a strain of rat with acoustically-evoked epileptic seizures (P77PMC rats), an extraordinarily strong analgesic effect was observed when EA of 100Hz was used; an effect similar to that in Wistar rats pre-treated with L-365,260. However, icv injected L-365,260 did not potentiate the analgesic effect induced by EA of any frequency in P77PMC rats. The results suggest that high frequency EA is more likely to increase the release of CCK-8 in the CNS as compared to low frequency EA; and also that P77PMC rats may have a functional deficit of the central CCK system probably due to a reduced rate of release of CCK-8 in the CNS, following EA stimulation.