Determination and characterization of the antinociceptive activity of intraventricularly administered acetylcholine in mice

Abstract

Antinociceptive activity of intraventricularly administered acetylcholine was quantitated in mice by the tail-flick and phenylquinone tests. Acetylcholine was administered intraventricularly under light ether anesthesia in a 5 mul volume of sterile saline and mice were retested 10 minutes after the operation. A dose-response curve was established for acetylcholine (ED50 equals 7.3 mug) which was potentiated by intraventricular neostigimine and blocked by intraperitoneal atropine, but not by atropine methyl nitrate or mecamylamine. The antinociceptive effect of morphine was potentiated by intraventricularly administered acetylcholine. The acetylcholine-induced antinocieption was blocked by five narcotic antagonists in the same rank order of potency in which they antagonized the effects of morphine. However, the stereo-specificity of two narcotic antagonists, pentazocine and cylcazocine, was reversed in blocking acetylcholine and morphine-induced antinociception. The results of this study have established a phenomenon of acetylcholine-induced antinociception and identified the central, muscarinic nature of this response. In addition, several experiments have demonstrated similarities between this phenomenon and morphine-induced antinociception. These data implicate the possible involvement of central cholinergic mechanisms in the antinociceptive action of morphine.