Morphine and endorphins modulate dopamine turnover in rat median eminence.

Abstract

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...

Interaction of peptides related to ACTH, MSH and β-LPH with neurotransmitters in the brain

“…were needed in order to obtain a significant effect on this parameter (Garcia-Sevilla et al, 1980). The ~-MPT-induced disappearance of dopamine from the cortex and from the median eminence was found to be decreased by D-Ala2-D-LeuS-enkephalin by Deyo et al (1979). This latter obserw~tion is in accordance with results of a microfluorometric study of the ct-MPT-induced disappearance of formaldehyde-induced catecholamine fluorescence from substructures of the median eminence.…”

“…Striatal dopamine turnover, as measured from the rate of dopamine disappearance following inhibition of tyrosine hydroxylase with ~-MPT, was found to be increased after the i.c.v, administration of 25 pg D-AlaZ-Met-enkephalinamide (Calderini et al, 1978) and D-Ala2-D-LeuS-enkephalin (Deyo et al, 1979). Schwarcz et al (1979), on the other hand, reported that Met-enkephalin, given as an i.c.v, infusion of approximately 50 pg over a period of one hr in a total volume of 60/21, did not affect the ~-MPT-induced disappearance of dopamine fluorescence from dopamine terminals in the caudate nucleus.…”

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

“…Systemically or locally administered synthetic and locally administered natural peptidic kappa-opioid receptor agonists (ie dynorphin) inhibit dopamine release in the mesolimbicmesocortical dopaminergic systems (Di Chiara and Imperato, 1988;Spanagel et al, 1990;Claye et al, 1997;Zhang et al, 2004a, b). While mu-and kappa-opioid receptor antagonists can each reverse these effects, neither administered alone have been shown to alter dopamine release in either rodent or non-human primate models (Deyo et al, 1979;Durham et al, 1996;Butelman et al, 2002). One possible exception is a positron emission tomography (PET) study in rats, which found increased binding potential in the striatum of the displaceable dopamine D1 ligand [ 11 C]SCH23,390 following acute but not chronic nalmefene administration (Unterwald et al, 1997).…”

From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

“…Opioids act on a hypothalamic level, although a direct effect on the pituitary has not been completely excluded (Enjalbert et al, 1979). Endogenous opioid peptides and synthetic opiates suppress TH activity and m-RNA levels in the TIDA neurons (Arbogast and Voogt, 1998;Deyo et al, 1979;Reymond et al, 1983;Andrews and Grattan, 2003). Therefore, one established mechanism of opioid-induced PRL secretion is through inhibition of TIDA neuronal activity, probably modulated by the opioid receptor subtypes m and k (see review, Ben-Jonathan, 1994;Soaje and Deis, 1994).…”