Evidence for a Spinal Site at Which Opioids May Act to Inhibit the Milk-ejection Reflex

Morphine was injected into the lumbar subarachnoid space of anaesthetized lactating rats (7-10 days post partum) to examine its effect on the milk-ejection reflex at a spinal level. Although the delay until the first milk-ejection response to the suckling of hungry pups was variable (3-60 min) the subsequent responses occurred at regular intervals of 7.5 +/- 0.4 min; milk-ejection responses were detected by measurement of intramammary pressure and by the characteristic behaviour of the pups. Injection of morphine (4-50 micrograms) via a cannula inserted into the spinal subarachnoid space inhibited reflex milk ejection in a dose-related manner without affecting the sensitivity of the mammary gland to exogenous oxytocin (1 mu., i.v.); injection extradurally was without effect. The opiate antagonist naloxone (10 micrograms), when injected intrathecally, did not significantly alter the pattern of reflex milk ejection or the amplitude of the intramammary pressure response, but prevented the inhibitory effect of morphine when administered with the opiate. Pethidine (250 and 400 micrograms) also inhibited the milk-ejection reflex. It is unlikely that the effect of spinal administration of morphine occurred as the result of the transportation to a supraspinal site since release of oxytocin evoked by intraventricular injection of hypertonic sodium chloride (3 mol/l) was blocked by intraventricular injection of morphine (4 micrograms) but not by a much larger dose (40 micrograms) injected intrathecally.