The effect of L-DOPA on milk ejection and on prolactin release during 30 min of suckling was studied in lactating rats. Various doses of L-DOPA (1-25, 2-5, 5 and 10 mg/100 g body wt) were injected i.p. 30 min before the suckling period. Control rats were injected with 0-9% NaCl solution only. An inhibition of milk ejection proportional to the dose of drug administered was obtained. The dose of 10 mg completely blocked milk ejection but 1-25 mg had no effect. A normal milk-ejection response was obtained with a small dose of oxytocin injected immediately before nursing into mothers treated with 10 mg L-DOPA, indicating that the blocking effect was not due to a lack of mammary gland response. In control mothers, serum prolactin levels increased from 67-2 +/- 25-9 (S.E.M.) to 950-3 +/- 118-7 ng/ml after a 30 min suckling period. L-DOPA (5 and 10 mg) prevented the release of prolactin induced by suckling, but 1-25 and 2-5 mg L-DOPA had no effect. The results indicate that oxytocin and prolactin release induced by suckling in lactating rats is inhibited by an increase of catecholamines at the hypothalamic-hypophysial axis.

SUMMARY1. Recordings were made from a total of fifty-three neurones in the supraoptic nuclei of four groups of rats: intact rats, animals in which the hypothalamus had been partly denervated by anteriorly or posteriorly placed semicircular cuts, and rats with a totally deafferented hypothalamus. 4. The results imply that under the conditions ofthese experiments the spontaneous activity of the supraoptic nucleus in intact animals was maintained by an extrahypothalamic excitatory input, that partial hypothalamic isolation reduced its intensity, possibly by unmasking an inhibitory input, and that total isolation reduced it to an even greater extent. Osmotic activation of supraoptic cells was only possible when the anterior connexions of the hypothalamus were intact. Thus the cerebral osmoreceptors for vasopressin release may be situated outside the supraoptic nuclei.

The effect of prostaglandin F2 alpha (PGF2alpha) on milk ejection and on oxytocin release during suckling for one or two periods of 30 min was studied in lactating rats. Doses of PGF2 alpha (20 or 40 phi g) were injected i.p. 15 min before the suckling period. Control rats were injected with physiological saline. An inhibition of milk ejection proportional to the dose of drug administered was obtained. A normal milk ejection response was induced with a small dose of oxytocin injected immediately before nursing to mothers treated with PGF2 alpha, indicating that the blocking effect was not due to a lack of mammary gland response. Two groups of mothers were injected with 40 phi g PGF2 alpha 2 and 4 h respectively before suckling. In both groups milk ejection was partially but significantly inhibited. In rats pre-treated with sodium pentobarbitone (3-5 mg/100 g body wt) to prevent the release of oxytocin induced by suckling, PGF2 alpha (10 or 20 phi g) did not modify the inhibition of milk ejection indicating that PGF2 alpha does not have milk-ejecting activity. The administration of oxytocin to anaesthetized rats, immediately before a second suckling period, induced a normal milk-ejection response while in the rats treated with PGF2 alpha, oxytocin was less effective. The results indicate that PGF2 alpha inhibited milk ejection by a central block on oxytocin release and that the lipid is not able to mimic peripherally the milk-ejecting activity of oxytocin.

In a previous paper (Prilusky & Deis, 1975) a blocking effect of l-DOPA on milk ejection and on prolactin release was demonstrated in lactating rats. The inhibitory effect of brain catecholamines on prolactin release is well established and it is probably mediated through dopamine (MacLeod, 1969; Donoso, Bishop, Fawcett, Krulich & McCann, 1971). Since a catecholaminergic system in the central nervous system may regulate prolactin release in lactating rats, we investigated the effect of the suckling stimulus on prolactin release in rats treated with l-DOPA.White primiparous lactating rats weighing about 270 g were used. Each litter was reduced to six young 4 days after birth. On the 10th day of lactation, the litter was separated from the mother in the early morning for 9 hr. The young were returned at 15.00 hours and allowed to suck for 30 min. The young were weighed to the nearest 0\ m=. \ 1 g immediately before and after the suckling period to determine the amount of milk ejected by the mother. The procedure was repeated on 2 consecutive days and on the 3rd day blood samples were obtained, one from each rat, by heart puncture without anaesthesia at various times after the end of the suckling period. This simple method takes only a few seconds and does not disturb the rats (Vermouth & Deis, 1974).Rats in Group 1 were injected i.p. with l,3-4-dihydroxyphenylalanine (l-DOPA: Regis Chemicals; 10 mg/100 g body wt) suspended in physiological saline 30 min before the suckling period. The serum prolactin levels at 0, 30, 60, 90, 120, 150, 180 and 210 min after the suckling period were measured by radioimmunoassay with two dose levels of serum (Niswender, Chen, Midgley, Meites & Ellis, 1969) and reagents supplied by the NIAMDD. All the serum samples were assessed in a single radioimmunoassay to eliminate between-assay variation. Student's t test was used to assess the level of significance.The normal release of prolactin induced by suckling was prevented by l-DOPA during the first 90 min after suckling (Text- fig. 1). A peak in serum prolactin concentration was obtained at 120 min (P<0-001). At 150 min serum prolactin was still significantly higher than the pre-suckling values of control rats (P<0005), but a progressive decrease occurred at 180 and 210 min after the suckling period. The mean values at 180 and 210 min were not significantly different from the control presuckling level and the levels obtained in the first 90 min after suckling in the treated rats.In order to see if the peak serum prolactin level obtained 120 and 150 min after the suckling period in rats treated with L-DOPA was due to the suckling stimulus and was not a secondary effect of L-DOPA at the central nervous system, rats in Group 2 were similarly treated with l-DOPA but the suckling stimulus was omitted. The serum prolactin concentration was estimated at 90, 180, 210 and 270 min after the l-DOPA injection, corresponding to the 30,120,150 and 210 min times for the Group 1 rats. At none of the times studied was the serum prolactin level significa...

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