comparison of the effects of acute and repeated morphine administration on fast synaptic transmission in magnocellular neurons of supraoptic nucleus, plasma vasopressin levels, and urine volume of male rats

The activity of the magnocellular neurons [MCNs] of supraoptic nucleus [SON] is regulated by a variety of excitatory and inhibitory inputs. Opioids are one of the important compounds that affect these inputs at SON synapses. In this study, whole-cell patch clamp recording of SON neurons was used to investigate the effect of acute and repeated morphine administration on spontaneous inhibitory and excitatory post synaptic currents [sIPSCs and sEPSCs] in MCNs. While acute bath application of morphine to brain slice of intact rat produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency, repeated in vivo administration of morphine produced opposite effect. Moreover, repetitive i.c.v. administration of morphine for three consecutive days caused significant increase in urine volume, but had no significant alteration in water consumption compared to control group. The increase in urine volume was consistent with a significant decrease in plasma arginine vasopressin [AVP] levels after repetitive i.p. morphine administration. The results suggest that acute administration of morphine stimulates whereas repeated administration of morphine inhibits the MCNs. Morphine-induced MCN inhibition could result in diminished plasma AVP levels and eventually an increase in urine volume of rats

Blockade of opioid receptors located in the rat nucleus cuneiformis reduced the antinociceptive responses of local but not systemic administration of morphine in formalin test

Previous studies have shown the role of opioid receptors located in the nucleus cuneiformis [CnF] in acute pain, but not in chronic pain models. In the present study, we have determined that possible effects of these receptors at the CnF on both early and late phases of formalin test following local and systemic morphine administration. Each rat was given a subcutaneous 50-p.1 injection of 2.5% formalin into plantar surface of hind paw. Ninety five Wistar rats bilaterally received morphine [1, 2, 4 and 8 p.g/0.3 p.1 saline per side] into the CnF, just before the formalin test. Naloxone [I p.g/0.3 p1 saline per side] was also microinjected 2 minutes before local or 28 minutes after intraperitoneal administration of morphine. The results showed that bilateral intra-CnF administration of morphine dose-dependently produced analgesia in formalin test. Naloxone administration into the CnF antagonized the analgesic response induced by morphine [4 p.g/0.3 p.1 saline] microinjection. The results also showed that analgesic effect of systemic morphine was not significantly decreased by naloxone microinjection. We suggest that the opioid receptors located in the CnF, in part, indirectly affect the morphine-induced descending pain modulatory circuit