Opioids and Coupling of the Anterior Peri-Third Ventricular Input to Oxytocin Neurones in Anaesthetized Pregnant Rats

In the pregnant rat the osmotic drive to oxytocin neurones is reduced and oxytocin secretion itself is inhibited by endogenous opioids. Coupling of the anterior peri-third ventricular input pathway, involved in osmoregulation, to magnocellular oxytocin neurones was studied in urethane-anaesthetized virgin and 21 day pregnant rats using electrical stimulation of the region anterior and ventral to the third cerebral ventricle (AV3V region) to drive the oxytocin neurones, and giving naloxone to prevent the action of any endogenous opioids on the system. Trains ofstimuli (0.5 mA, 1 ms pulses, 10 s on 10 s off, at either 10 Hz or 25 Hz for 10 or 2 min respectively) were given at 20 or 30 min intervals via an electrode stereotaxically-implanted in the AV3V region, and femoral arterial blood plasma samples collected immediately before and after each stimulation were radioimmunoassayed for oxytocin concentration. The first (control) AV3V stimulation increased plasma oxytocin concentration reproducibly and similarly in virgin and 21-day pregnant rats. Naloxone administered 10 min before the second stimulus increased basal plasma oxytocin concentration in virgin and pregnant rats and increased the oxytocin secretory response to 25 Hz AV3V stimulation in virgin but not pregnant rats, and the response was significantly greater in virgin rats. Naloxone reveals oxytocin secretion unrestrained by endogenous opioids, therefore it appears that there is an opioid-independent reduction in the excitatory coupling of the AV3V input to oxytocin neurones which may explain the reduced osmoresponsiveness of oxytocin neurones at the end of pregnancy. In other experiments, morphine (μ-opioid agonist; at 1 & 5 mg/kg 5 min before the second and third stimulation periods respectively) or U50,488 (κ-opioid agonist; 0.5 and 2.5 mg/kg respectively) was given to test the opioid sensitivity of the oxytocin neurone response to stimulation of the AV3V input. Morphine did not significantly affect the oxytocin secretory response to 25 Hz AV3V stimulation in either virgin or pregnant rats but there was a significant dose related inhibition of the oxytocin secretory response to 10 Hz stimulation in both groups. U50,488 also inhibited the oxytocin secretory response to 25 Hz AV3V stimulation in a dose-related manner in both virgin and pregnant rats. The inhibitory effects of morphine and U50,488 were not different between virgin and pregnant rats; this indicates that central opioid interactions with the AV3V input to oxytocin neurones are not changed in pregnancy. The initial similar oxytocin secretory response to AV3V stimulation in pregnant and virgin rats seems to be a product of a reduced effectiveness of the excitatory AV3V input to oxytocin neurones in late pregnancy and the previously established reduced posterior pituitary sensitivity to inhibitory endogenous opioids.