The effects of the cholecystokinin antagonist, proglumide, on prolactin secretion in the rat

Since cholecystokinin produced important effects on prolactin secretion following its intraventricular injection in ovariectomized rats, we have evaluated the effects of the cholecystokinin antagonist, proglumide, to assess the physiologic significance of CCK in the control of prolactin release. Conscious rats of either sex were used following implantation of third ventricular and/or intravenous cannulae for the administration of proglumide. Blood samples were drawn from conscious animals at various times after injection of the compound. Intraventricular injection of 1 or 10 micrograms of proglumide produced a dramatic decline in plasma prolactin levels in either castrate or intact male rats. Similar results were found following the intravenous injection of 10 or 100 micrograms of the drug. These results contrasted sharply with the findings in ovariectomized females in which the intraventricular injection of the same two doses of proglumide used in males produced a dose-related elevation of prolactin which was opposite to the delayed lowering of prolactin following the intravenous injection of the same doses of the compound used in males. These results indicate that proglumide can lower prolactin in male rats and suggests a physiologically significant role of CCK in the control of prolactin secretion in the male. There appears to be a sex difference in the response since the results contrasted sharply in ovariectomized female rats. The results in the females are puzzling and it is apparent that further studies are needed to determine whether or not CCK has a physiologically significant role to play in prolactin secretion in the female. Since previous results have shown that CCK has no effect on the release of prolactin by the pituitary directly these interactions are presumably taking place in the hypothalamus.