Influence of hemicholinium (HC-3) on morphine analgesia, tolerance, physical dependence and on brain acetylcholine

Administration of HC-3 intracerebrally at a dose which reduced brain acetylcholine (ACh) without any change in choline (Ch) levels antagonized morphine antinociception slightly as measured by inhibition of the tail-flick response, in both naive mice and in mice rendered tolerant to and dependent on morphine by pellet implantation. However, the development of tolerance to morphine and of dependence on morphine were not affected by HC-3. Although naloxone precipitated withdrawal jumping was enhanced irrespective of whether the HC-3 was administered before or after the dependence on morphine had developed, body weight loss during abrupt withdrawal was unaffected by HC-3. The results indicate that although some of the acute and withdrawal effects of morphine may be associated either directly or indirectly with acetylcholine, these actions do not appear to be the primary process responsible for initiating the development of tolerance and dependence.