European Journal of Pharmacology, 110 (1985) 143-146 143 Elsevier Short communication PHENCYCLIDINE-INDUCED INHIBITION OF RAT PROLACTIN SECRETION: INCREASED PORTAL BLOOD DOPAMINE HERBERT Y. MELTZER *, MILJANA SIMONOVIC and GARY A. GUDELSKY University of Chicago Pritzker School of Medicine, Department of Psychiatry and the Illinois State Psychiatric Institute, Chicago, U.S.A. Received 11 December 1984, accepted 29 January 1985 H.Y. MELTZER, M. SIMONOVIC and G.A. GUDELSKY, Phencyclidine-induced inhibition of rat prolactin secretion: increased portal blood dopamine, European J. Pharmacol. 110 (1985) 143-146. Intraperitoneal administration of phencyclidine (PCP, 2.5-20 mg/kg) produced a dose-related inhibition of the increase in serum PRL concentrations produced by a-methylparatyrosine (AMPT) or reserpine, but not morphine. Phencyclidine was more potent in antagonizing the PRL-releasing effect of reserpine than that of AMPT, suggesting a greater effect of PCP on the cytoplasmic than the storage dopamine (DA) pool. Phencyclidine had no effect on PRL release from rat pituitary glands in vitro. Intravenous administration of PCP (10 mg/kg) to anesthetized male rats produced a two-fold increase in pituitary stalk (DA) concentrations, suggesting that PCP inhibits rat serum PRL by increasing the release of DA from the tuberoinfundibular neurons, and possibly by blocking its reuptake as well. Dopamine Phencyclidine Prolactin 1. Introduction There is considerable behavioral and neuro- chemical evidence that phencyclidine (PCP) is an indirect dopamine (DA) agonist, inhibiting DA uptake (Doherty et al., 1980) and facilitating DA release (Vickroy and Johnson, 1982). However, there are conflicting data concerning the relative importance of vesicular and cytoplasmic DA pools as the sites of action of the DA releasing effect of PCP with some evidence favoring vesicular DA stores (Doherty et al., 1980) and other evidence, cytoplasmic DA (Vickroy and Johnson, 1982). Rat prolactin (PRL) secretion is tonically in- hibited by DA released from the tuberoinfundibu- lar dopaminergic (TIDA) neurons into the hypo- physeal portal circulation (Gudelsky and Porter, 1979a). We have previously reported that PCP, in accord with its proposed indirect DA agonist ac- tion, inhibits the increase in rat serum PRL con- * To whom all correspondence should be addressed: Univer- sity of Chicago, Department of Psychiatry, 5841 S. Maryland Avenue, Chicago, Illinois 60637, U.S.A. centrations produced by a-methylparatyrosine (AMPT), an inhibitor of DA synthesis (Meltzer et al., 1979). In order to further assess the indirect DA agonist properties of PCP, we have compared the ability of PCP to inhibit the increase in PRL secretion in reserpine-, AMPT- and morphine-pre- treated rats. The aim of these experiments was to determine the relative importance of granular DA stores, cytoplasmic DA, and impulse-dependent DA release for PCP-induced inhibition of rat PRL secretion. In addition, to further clarify where and how PCP is acting in this paradigm we have tested the ability of PCP to inhibit PRL release in vitro and to influence DA concentration in pituitary stalk plasma. 2. Materials and methods 2.1. Animals Male, Sprague-Dawley rats, purchased from Sprague-Dawley, Inc., Madison, WI, weighing from 200-250 g were used in all experiments. They 0014-2999/85/$03.30 © 1985 ElsevierScience Publishers B.V.