There is evidence that some of the actions of both endogenous and exogenous opioids (e.g., stimulation of prolactin release) are mediated by interaction with catecholaminergic systems. Morphine (1.67, 5, and 15 mg/kg of body weight, intraperitoneally) altered dopamine turnover as measured by the a-methyl-p-tyrosine method in the median eminence, neostriatum, and frontal cortex of male Sprague-Dawley rats. The turnover rate of dopamine was reduced in the median eminence and frontal cortexbut accelerated in the neostriatum. In the frontal cortex all doses were effective in decreasing dopamine turnover; however, in the median eminence the lowest dose of morphine did not significantly alter dopamine turnover. All three doses accelerated dopamine turnover in the neostriatum. Naloxone effectively reversed the effects of morphine at all doses in all brain areas, whereas it had no effect on turnover when given alone. In the median eminence, neostriatum, and frontal cortex, intraventricular injection of D-Ala2,D-Leu5J enkephalin (25 Mug) or fl-endorphin (15 ,g) produced the same effects on dopamine turnover as morphine. The actions of these peptides were blocked by naloxone. It is hypothesized that opiates and opioid peptides increase prolactin release by reducing the activity of the tuberoinfundibular dopaminergic system.Since the discovery of the endorphins and the enkephalins, peptides with opiate agonist activity, intensive investigations have been carried out in order to define the functions of these peptides in the nervous system. It is becoming evident that one such important role may be in the control of the release of hormones from the pituitary gland. It is well known from previous investigations on the pharmacology of narcotics that narcotic drugs affect the secretion of several pituitary hormones, including prolactin, growth hormone, vasopressin, and adrenocorticotropic hormone (ACTH). Morphine is a potent releaser of prolactin, growth hormone, and vasopressin (1-4). Recently, it has been shown that enkephalin analogs can also increase blood prolactin levels (5).Immunohistochemical studies on enkephalin distribution within the brain have defined several potential enkephalinergic pathways that may serve to regulate the release of these hormones (6). Thus, an enkephalin-containing neuronal system projecting from the paraventricular nucleus of the hypothalamus to the pars nervosa of the pituitary may serve to regulate the release of vasopressin (7). In addition, it has been shown that the median eminence contains a large number of enkephalinergic nerve endings (6). Because it is known that endorphins and morphine do not produce their releasing actions on pituitary prolactin by direct action on pituitary lactotrophs (8, 9), it therefore appears that this action of these opioid compounds is mediated at the level of the hypothalamus.Because the main hypothalamic control of prolactin secretion is mediated by hypothalamic dopaminergic neurons (10), we investigated the possibility that the releasing effects of...