Mechanisms of intestinal dysmotility in morphine dependence: whether central or peripheral?

Changes of intestinal motility and transit due to morphine administration are attributed to its central and peripheral action, however coexistence of both central and peripheral mu receptors in morphine dependence hasn't been clearly demonstrated so far. Our purpose was the evaluation of the effect of either CNS or ENS mu receptor blockade on intestinal motility in morphine dependent rats. Twenty male rats were subjected to chronic subcutaneous morphine infusions for 72 hrs. On each day motility indices (MI) were analysed in the animals' duodenum and ascending colon before and after either intraperitoneal (IP) or intracerebroventricular (ICV) mu antagonist (CTOP) administration. Tolerance of the intestinal motility to morphine developed in both the duodenum and the ascending colon after 72 hrs of the infusion. Dependence was observed at 24 hrs and maintained at 48 and 72 hrs of morphine administration. On each day no differences of MI reaction to mu blockade were visible regarding the IP or ICV CTOP administration. Our results suggest the involvement of both the CNS and the ENS mu opioid receptors in mechanisms of the intestinal tolerance to and dependence upon morphine.