Abstract
Mu-opioid receptor (MOR) and opioid receptor-like receptor (ORL-1) circuits in the limbic hypothalamic system are important for the regulation of sexual receptivity in the female rat. Sexual receptivity is tightly regulated by the sequential release of estrogen and progesterone from the ovary suggesting ovarian steroids regulate the activity of these neuropeptide systems. Both MOR and ORL-1 distributions overlap with the distribution of estrogen and progesterone receptors in the hypothalamus and limbic system providing a morphological substrate for interaction between steroids and the opioid circuits in the brain. Both MOR and ORL-1 are receptors that respond to activation by endogenous ligands with internalization into early endosomes. This internalization is part of the mechanism of receptor desensitization or down regulation. Although receptor activation and internalization are separate events, internalization can be used as a temporal measure of circuit activation by endogenous ligands. This review focuses on the estrogen and progesterone regulation of MOR and ORL-1 circuits in the medial preoptic nucleus and ventromedial nucleus of the hypothalamus that are central to modulating sexual receptivity.
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Dhawan B. N., F. Cesselin, R. Raghubir, T. Reisine, P. B. Bradley, P. S. Portoghese, and M. Hamon. (1996) International union of pharmacology.12. Classification of opioid receptors. Pharmacological Reviews 48, 567–592.
Reisine T. and G. I. Bell. (1993) Molecular biology of opioid receptors. Trends in Neurosciences 16, 506–510.
Chen Y., A. Mestek, J. Liu, J. A. Hurley, and L. Yu. (1993) Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Molecular Pharmacology 44, 8–12.
Thompson R. C., A. Mansour, H. Akil, and S. J. Watson. (1993) Cloning and pharmacological characterization of a rat mu-opioid receptor. Neuron 11, 903–913.
Wang J. B., P. S. Johnson, A. M. Persico, A. L. Hawkins, C. A. Griffin, and G. R. Uhl. (1994) Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett. 338, 217–222.
Mollereau C., M. Parmentier, P. Mailleux, J. L. Butour, C. Moisand, P. Chalon, D. Caput, G. Vassart, and J. C. Meunier. (1994) ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization. FEBS Lett. 341, 33–38.
Lachowicz J. E., Y. Shen, F. J. Monsma, Jr., and D. R. Sibley. (1995) Molecular cloning of a novel G protein-coupled receptor related to the opiate receptor family. J. Neurochem. 64, 34–40.
Wang J. B., P. S. Johnson, Y. Imai, A. M. Persico, B. A. Ozenberger, C. M. Eppler, and G. R. Uhl. (1994) cDNA cloning of an orphan opiate receptor gene family member and its splice variant. FEBS Lett. 348, 75–79.
Zaki P. A., D. E. Keith, J. B. Thomas, F. I. Carroll, and C. J. Evans. (2001) Agonist-, antagonist-, and inverse agonist-regulated trafficking of the delta-opioid receptor correlates with, but does not require, G protein activation. Journal of Pharmacology and Experimental Therapeutics 298, 1015–1020.
Zaki P. A., D. E. Keith, G. A. Brine, F. I. Carroll, and C. J. Evans. (2000) Ligand-induced changes in surface mu-opioid receptor number: Relationship to G protein activation? Journal of Pharmacology and Experimental Therapeutics 292, 1127–1134.
Daaka Y., L. M. Luttrell, S. Ahn, G. J. DellaRocca, S. S. G. Ferguson, M. G. Caron, and R. J. Lefkowitz. (1998) Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. Journal of Biological Chemistry 273, 685–688.
Luttrell L. M., Y. Daaka, G. J. DellaRocca, and R. J. Lefkowitz. (1997) G protein-coupled receptors mediate two functionally distinct pathways of tyrosine phosphorylation in rat 1a fibroblasts—Shc phosphorylation and receptor endocytosis correlate with activation of Erk kinases. Journal of Biological Chemistry 272, 31,648–31,656.
Vieira A. V., C. Lamaze, and S. L. Schmid. (1996) Control of Egf Receptor Signaling by Clathrin-Mediated Endocytosis. Science 274, 2086–2089.
Ignatova E. G., M. M. Belcheva, L. M. Bohn, M. C. Neuman, and C. J. Coscia. (1999) Requirement of receptor internalization for opioid stimulation of mitogen-activated protein kinase: Biochemical and immunofluorescence confocal microscopic evidence. Journal of Neuroscience 19, 56–63.
Sternini C., N. C. Brecha, J. Minnis, G. D’Agostino, B. Balestra, E. Fiori, and M. Tonini. (2000) Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors. Neuroscience 98, 233–241.
Eckersell C. B., P. Popper, and P. E. Micevych. (1998) Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala. J. Neurosci. 18, 3967–3976.
Sinchak K. and P. E. Micevych. (2001) Progesterone blockade of estrogen activation of μ-opioid receptors regulates reproductive behavior. J Neurosci. 21, 5723–5729.
Lefkowitz R. J., S. Cotecchia, M. A. Kjelsberg, J. Pitcher, W. J. Koch, J. Inglese, and M. G. Caron. (1993) Adrenergic receptors: recent insights into their mechanism of activation and desensitization. Adv. Second Messenger Phosphoprotein Res. 28, 1–9.
Birnbaumer L. and A. M. Brown. (1990) G proteins and the mechanism of action of hormones, neurotransmitters, and autocrine and paracrine regulatory factors. Am. Rev. Respir. Dis. 141, S106–114.
Birnbaumer L., A. Yatani, A. M. VanDongen, R. Graf, J. Codina, K. Okabe, R. Mattera, and A. M. Brown. (1990) G protein coupling of receptors to ionic channels and other effector systems. Br. J. Clin. Pharmacol. 30 Suppl 1, 13S-22S.
Rories C. and T. C. Spelsberg. (1989) Ovarian steroid action on gene expression: mechanisms and models. Annu. Rev. Physiol. 51, 653–681.
McEwen B. S. (2001) Genome and hormones: Gender differences in physiology — Invited review: Estrogens effects on the brain: multiple sites and molecular mechanisms. Journal of Applied Physiology 91, 2785–2801.
Brown E. R., R. E. Harlan, and J. E. Krause. (1990) Gonadal steroid regulation of substance P (SP) and SP-encoding messenger ribonucleic acids in the rat anterior pituitary and hypothalamus. Endocrinology 126, 330–340.
Priest C. A., D. Borsook, S. E. Hyman, and D. W. Pfaff. (1995) Estrogen and stress interact to regulate the transcriptional activity of a proenkephalin promoter-beta-GAL fusion gene in the hypothalamus of transgenic mice. Soc. Neurosci. Abs. 21, 1364.
Priest C. A., C. B. Eckersell, and P. E. Micevych. (1995) Estrogen regulates preproenkephalin-A mRNA levels in the rat ventromedial nucleus: temporal and cellular aspects. Brain Res. Mol. Brain Res. 28, 251–262.
Uht R. M., C. M. Anderson, P. Webb, and P. J. Kushner. (1997) Transcriptional activities of estrogen and glucocorticoid receptors are functionally integrated at the AP-1 response element. Endocrinology 138, 2900–2908.
Akesson T. R. and P. E. Micevych. (1988) Evidence for an absence of estrogen concentration by CCK-immunoreactive neurons in the hypothalamus of the female rat. J. Neurobiol. 19, 3–16.
Shivers B. D., R. E. Harlan, J. I. Morrell, and D. W. Pfaff. (1983) Absence of oestradiol concentration in cell nuclei of LHRH-immunoreactive neurones. Nature 304, 345–347.
Watson R. E. (1992) Further evidence that most luteinizing hormone-releasing hormone neurons are not directly estrogen responsive. J. Neurosci. 4, 311–317.
Skynner M. J., J. A. Sim, and A. E. Herbison. (2001) Detection of estrogen receptor alpha and beta messenger ribonucleic acids in adult gonadotropin-releasing hormone neurons (vol 140, pg 5195, 1999). Endocrinology 142, 492.
Roy D., N. L. Angelini, and D. D. Belsham. (1999) Estrogen directly represses gonadotropin-releasing hormone (GnRH) gene expression in estrogen receptor-alpha (ERalpha)-and ERbeta-expressing GT1–7 GnRH neurons. Endocrinology 140, 5045–5053.
Nielsen D. A. and Shapiro D. J. (1990) Insights into hormonal control of messenger RNA stability. Molecular Endocrinology 4, 953–957.
Singh M., G. Setalo, Jr., X. Guan, D. E. Frail, and C. D. Toran-Allerand. (2000) Estrogen-induced activation of the mitogen-activated protein kinase cascade in the cerebral cortex of estrogen receptor-alpha knock-out mice. J. Neurosci. 20, 1694–1700.
Razandi M., A. Pedram, G. Greene, and E. Levin. (1999) Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERalpha and ERbeta expressed in Chinese hamster ovary cells. Mol. Endocrinol. 13, 307–319.
Razandi M., P. Oh, A. Pedram, J. Schnitzer, and E. R. Levin. (2002) ERs associate with and regulate the production of caveolin: Implications for signaling and cellular actions. Mol. Endocrinol. 16, 100–115.
Wade S. B., P. Oommen, W. C. Conner, D. J. Earnest, and R. C. Miranda. (1999) Overlapping and divergent actions of estrogen and the neurotrophins on cell fate and p53-dependent signal transduction in conditionally immortalized cerebral cortical neuroblasts. J. Neurosci. 19, 6994–7006.
Toran-Allerand C. D. (1995) Developmental interactions of estrogens with the neurotrophins and their receptors, in Neurobiological Effects of Sex Steroid Hormones (Micevych P. E. and Hammer R. P., Jr., eds.), Cambridge University Press, pp. 391–411.
Revelli A., M. Massobrio, and J. Tesarik. (1998) Nongenomic actions of steroid hormones in reproductive tissues. Endocrine Reviews 19, 3–17.
Chaban V., E. A. Mayer, H. S. Ennes, and P. E. Micevych. Estradiol inhibits ATP-induced [Ca2+]i increase in DRG. Neuroscience (In Press).
Moss R. L., Q. Gu, and M. Wong. (1997) Estrogen: nontranscriptional signaling pathway. Recent Prog. Horm. Res. 52, 33–68.
Kelly M. and E. Wagner. (1999) Estrogen modulation of G-protein-coupled receptors. Trends in Endocrinology and Metabolism 10, 369–374.
Nadal A., M. Diaz, and M. A. Valverde. (2001) The estrogen trinity: Membrane, cytosolic, and nuclear effects. News in Physiological Sciences 16, 251–255.
Clemens L. G. and D. R. Weaver. (1985) The role of gonadal hormone in the activation of feminine sexual behavior, in Handbook of Behavioral Neurobiology (Adler N., Pfaff D. and Goy R. W., eds.), Plenum Press, New York, pp. 183–227.
Bloch G. J., A. M. Babcock, R. A. Gorski, and P. E. Micevych. (1987) Cholecystokinin stimulates and inhibits lordosis behavior in female rats. Physiol. Behav. 39, 217–224.
Mani S. K., J. D. Blaustein, and B. W. Omalley. (1997) Progesterone receptor function from a behavioral perspective. Hormones and Behavior 31, 244–255.
Blaustein J. D., R. Finkbohner, and Y. Delville. (1987) Estrogen-induced and estrogen-facilitated female rat sexual behavior is not mediated by progestin receptors. Neuroendocrinology 45, 152–159.
Quadagno D. M., J. McCullough, and R. Langan. (1972) The effect of varying amounts of exogenous estradiol benzoate on estrous behavior in the rat. Horm. Behav. 3, 175–179.
Boling J. L. and R. J. Blandau. (1939) The estrogen-progesterone induction of mating responses in the spayed female rat. Endocrinology 25, 359–364.
Sirinathsinghji D. J. S. (1986) Regulation of lordosis behavior in the female rat by corticotropin-releasing factor, beta-endorphin/corticotropin and luteinizing hormone-releasing hormone neuronal systems in the medial preoptic area. Brain Res. 375, 149–156.
Pfaus J. G. and D. W. Pfaff. (1992) Mu-, delta-, and kappa-opioid receptor agonists selectively modulate sexual behaviors in the female rat: differential dependence on progesterone. Horm. Behav. 26, 457–473.
Sirinathsinghji D. J. (1984) Modulation of lordosis behavior of female rats by naloxone, beta-endorphin and its antiserum in the mesencephalic central gray: possible mediation via GnRH. Neuroendocrinology 39, 222–230.
Sirinathsinghji D. J. (1985) Modulation of lordosis behaviour in the female rat by corticotropin releasing factor, beta-endorphin and gonadotropin releasing hormone in the mesencephalic central gray. Brain Research 336, 45–55.
Acosta-Martinez M. and A. M. Etgen. (2002) Activation of mu-opioid receptors inhibits lordosis behavior in estrogen and progesterone-primed female rats. Hormones and Behavior 41, 88–100.
Wiesner J. B. and R. L. Moss. (1984) Beta-endorphin suppression of lordosis behavior in female rats; lack of effect of peripherally-administered naloxone. Life Sciences 34, 1455–1462.
Torii M. and K. Kubo. (1994) The effects of intraventricular injection of beta-endorphin on initial estrogen action to induce lordosis behavior. Physiol. Behav. 55, 157–162.
Torii M., K. Kubo, and T. Sasaki. (1995) Naloxone and initial estrogen action to induce lordosis in ovariectomized rats: the effect of a cut between the septum and preoptic area. Neurosci. Lett. 195, 167–170.
Torii M., K. Kubo, and T. Sasaki. (1996) Influence of opioid peptides on the priming action of estrogen on lordosis in ovariectomized rats. Neurosci. Lett. 212, 68–70.
Mansour A., C. A. Fox, R. C. Thompson, H. Akil, and S. J. Watson. (1994) Mu-opioid receptor mRNA expression in the rat CNS: comparison to mu-receptor binding. Brain Res. 643, 245–265.
Mansour A., C. A. Fox, S. Burke, H. Akil, and S. J. Watson. (1995) Immunohistochemical localization of the cloned mu opioid receptor in the rat CNS. J. Chem. Neuroanat. 8, 283–305.
Pfaff D. W., S. Schwartz-Giblin, M. McCarthy, and L. M. Kow. (1994) Cellular and molecular mechanisms of female reproductive behaviors, in The Physiology of Reproduction (Knobil E. and Neill J. D., eds.), Raven Press, Ltd, New York, pp. 107–220.
Bunzow J. R., C. Saez, M. Mortrud, C. Bouvier, J. T. Williams, M. Low, and D. K. Grandy. (1994) Molecular cloning and tissue distribution of a putative member of the rat opioid receptor gene family that is not a mu, delta or kappa opioid receptor type. FEBS Lett. 347, 284–288.
Meunier J. C. (1997) Nociceptin/orphanin FQ and the opioid receptor-like ORL1 receptor. European Journal of Pharmacology 340, 1–15.
Meunier J. C., C. Mollereau, L. Toll, C. Suaudeau, C. Moisand, P. Alvinerie, J. L. Butour, J. C. Guillemot, P. Ferrara, B. Monsarrat, et al. (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor Nature 377, 532–535.
Reinscheid R. K., H. P. Nothacker, A. Bourson, A. Ardati, R. A. Henningsen, J. R. Bunzow, D. K. Grandy, H. Langen, F. J. Monsma, Jr., and O. Civelli. (1995) Orphanin FQ: A neuropeptide that activates an opioid-like G protein-coupled receptor. Science 270, 792–794.
Sinchak K., D. G. Hendricks, R. Baroudi, and P. E. Micevych. (1997) Orphanin FQ/nociceptin in the ventromedial nucleus facilitates lordosis in female rats. Neuroreport 8, 3857–3860.
Darland T., M. M. Heinricher, and D. K. Grandy. (1998) Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more. Trends in Neuroscience 21, 215–221.
Sinchak K., H. E. Romeo, and P. E. Micevych. (2001) Estrogen and progestin regulation of OFQ/nociceptin and ORL-1 mRNA expression in the female rat limbic hypothalamic system. Soc. Neurosci. Abstr. 27, 424.4.
Lee N. M. and A. P. Smith. (1980) A protein-lipid model of the opiate receptor. Life Sci. 26, 1459–1464.
Patterson S. J., L. E. Robson, and H. W. Kosterlitz. (1983) Classification of opiate receptors. Br. Med. Bull. 39, 31–36.
Smith A., N. Lee, and H. Loh. (1983) The multiple-site beta-endorphin receptor. Trends Pharmacol. Sci. 4, 163–164.
Law P. Y. and H. H. Loh. (1999) Regulation of opioid receptor activities. Journal of Pharmacology and Experimental Therapeutics 289, 607–624.
Zadina J. E., L. Hackler, L. J. Ge, and A. J. Kastin. (1997) A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386, 499–502.
Harrison C., S. McNulty, D. Smart, D. J. Rowbotham, D. K. Grandy, L. A. Devi, and D. G. Lambert. (1999) The effects of endomorphin-1 and endomorphin-2 in CHO cells expressing recombinant mu-opioid receptors and SH-SY5Y cells. British Journal of Pharmacology 128, 472–478.
Finley J. C., P. Lindstrom, and P. Petrusz. (1981) Immunocytochemical localization of beta-endorphin-containing neurons in the rat brain. Neuroendocrinology 33, 28–42.
Hammer R. P. and S. Cheung. (1995) Sex steroid regulation of hypothalamic opioid function, in Neurobiological Effects of Sex Steroid Hormones (Micevych P. E. and Hammer R. P., eds.), Cambridge University Press, New York, NY, pp. 143–159.
Priest C. A. and J. L. Roberts. (2000) Estrogen and tamoxifen differentially regulate beta-endorphin and cFos expression and neuronal colocalization in the arcuate nucleus of the rat. Neuroendocrinology 72, 293–305.
Wilcox J. N. and J. L. Roberts. (1985) Estrogen decreases rat hypothalamic proopiomelanocortin messenger ribonucleic acid levels. Endocrinology 117, 2392–2396.
Petersen S. L., M. L. Keller, S. A. Carder, and S. McCrone. (1993) Differential Effects of Estrogen and Progesterone on Levels of POMC Messenger RNA Levels in the Arcuate Nucleus—Relationship to the Timing of LH Surge Release. Journal of Neuroendocrinology 5, 643–648.
Wise P. M., K. Scarbrough, N. G. Weiland, and G. H. Larson. (1990) Diurnal pattern of proopiomelanocortin gene expression in the arcuate nucleus of proestrous, ovariectomized, and steroid-treated rats: a possible role in cyclic luteinizing hormone secretion. Mol. Endocrinol. 4, 886–892.
Cheung S. and R. Hammer. (1995) Gonadal steroid hormone regulation of proopiomelanocortin gene expression in the arcuate neurons that innervate the medial preoptic are of the rat. Neuroendocrinology 62, 283–292.
Ge F., R. P. Hammer, Jr., and S. A. Tobet. (1993) Ontogeny of Leu-enkephalin and beta-endorphin innervation of the area in male and female rats. Brain Res. Dev. Brain Res. 73, 273–281.
Micevych P. E., C. B. Eckersell, N. Brecha, and K. Holland. (1997) Estrogenic modulation of opiate and cholecystokinin systems in the limbic-hypothalamic circuit. Brain Res. Bull. 44, 335–343.
Morrell J. I., J. F. McGinty, and D. W. Pfaff. (1985) A subset of beta-endorphin- or dynorphin-containing neurons in the medial basal hypothalamus accumulates estradiol. Neuroendocrinology 41, 417–426.
Jirikowski G. F., I. Merchenthaler, G. E. Rieger, and W. E. Stumpf. (1986) Estradiol target sites immunoreactive for beta-endorphin in the arcuate nucleus of rat and mouse hypothalamus. Neurosci. Lett. 65, 121–126.
Simonian S. X., D. P. Spratt, and A. E. Herbison. (1999) Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. Journal of Comparative Neurology 411, 346–358.
Fodor M. and H. A. Delemarre-van de Waal. (2001) Are POMC neurons targets for sex steroids in the arcuate nucleus of the rat? Neuroreport 12, 3989–3991.
Shughrue P. J., M. V. Lane, and I. Merchenthaler. (1997) Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. Journal of Comparative Neurology 388, 507–525.
Priest C. A., D. Borsook, and D. W. Pfaff. (1997) Estrogen and stress interact to regulate the hypothalamic expression of a human proenkephalin promoter-beta-galactosidase fusion gene in a site-specific and sex-specific manner. J. Neuroendocrinol. 9, 317–326.
Sinchak K., C. Eckersell, V. Quezada, A. Norell, and P. Micevych. (2000) Preproenkephalin mRNA levels are regulated by acute stress and estrogen stimulation. Physiol Behav. 69, 425–432.
Lopezcalderon A., C. Ariznavarreta, and C. L. C. Chen. (1991) Influence of Chronic Restraint Stress on Proopiomelanocortin Messenger RNA and Beta-Endorphin in the Rat Hypothalamus. Journal of Molecular Endocrinology 7, 197–204.
Zhou Y., R. Spangler, C. E. Maggos, X. M. Wang, J. S. Han, A. Ho, and M. J. Kreek. (1999) Hypothalamic-pituitary-adrenal activity and pro-opiomelanocortin mRNA levels in the hypothalamus and pituitary of the rat are differentially modulated by acute intermittent morphine with or without water restriction stress. Journal of Endocrinology 163, 261–267.
Martin-Schild S., A. A. Gerall, A. J. Kastin, and J. E. Zadina. (1999) Differential distribution of endomorphin 1- and endomorphin 2-like immunoreactivities in the CNS of the rodent. Journal of Comparative Neurology 405, 450–471.
Pierce T. L. and M. W. Wessendorf. (2000) Immunocytochemical mapping of endomorphin-2-immunoreactivity in rat brain. J. Chem. Neuroanat. 18, 181–207.
Wang Q. P., J. E. Zadina, J. L. Guan, and S. Shioda. (2002) Morphological studies of the endomorphinergic neurons in the central nervous system. Japanese Journal of Pharmacology 89, 209–215.
Zadina J. E. (2002) Isolation and distribution of endomorphins in the central nervous system. Japanese Journal of Pharmacology 89, 203–208.
Romano G. J., A. Krust, and D. W. Pfaff. (1989) Expression and estrogen regulation of progesterone receptor mRNA in neurons of the mediobasal hypothalamus: an in situ hybridization study [published erratum appears in Mol. Endocrinol 1989 Aug;3(11):1860]. Mol. Endocrinol. 3, 1295–1300.
Romano G. J., R. E. Harlan, B. D. Shiverst, R. D. Howells, and D. W. Pfaff. (1988) Estrogen increases proenkephalin messenger ribonucleic acid levels in the ventromedial hypothalamus of the rat. Mol. Endocrinol. 2, 1320–1328.
Holland K., A. Norell, and P. Micevych. (1998) Interaction of thyroxine and estrogen on the expression of estrogen receptor alpha, cholecystokinin, and preproenkephalin messenger ribonucleic acid in the limbic-hypothalamic circuit. Endocrinology 139, 1221–1228.
Eckersell C. B., C. A. Priest, and P. E. Micevych. (1994) Temporal regulation of preproenkephalin-A mRNA expression by estrogen in the posterior dorsal medial amygdala of the female rat. Society for Neuroscience 20, 1770.
Akesson T. R. and P. E. Micevych. (1991) Endogenous opioid-immunoreactive neurons of the ventromedial hypothalamic nucleus concentrate estrogen in male and female rats. J. Neurosci. Res. 28, 359–366.
Reinscheid R. K., J. Higelin, R. A. Henningsen, F. J. Monsma, and O. Civelli. (1998) Structures that delineate orphanin FQ and dynorphin A pharmacological selectivities. Journal of Biological Chemistry 273, 1490–1495.
Dooley C. T. and R. A. Houghten. (1996) Orphanin FQ: receptor binding and analog structure activity relationships in rat brain. Life Sci. 59, L23–29.
Reinscheid R. K., A. Ardati, F. J. Monsma, and O. Civelli. (1996) Structure-activity relationship studies on the novel neuropeptide orphanin FQ. Journal of Biological Chemistry 271, 14,163–14,168.
Shimohigashi Y., R. Hatano, T. Fujita, R. Nakashima, T. Nose, T. Sujaku, A. Saigo, K. Shinjo, and A. Nagahisa. (1996) Sensitivity of opioid receptor-like receptor ORL1 for chemical modification on nociceptin, a naturally occurring nociceptive peptide. J. Biol. Chem. 271, 23,642–23,645.
Ardati A., R. A. Henningsen, J. Higelin, R. K. Reinscheid, O. Civelli, and F. J. Monsma. (1997) Interaction of [H-3]orphanin FQ and I-125-Tyr14-orphanin FQ with the orphanin FQ receptor: Kinetics and modulation by cations and guanine nucleotides. Molecular Pharmacology 51, 816–824.
Butour J. L., C. Moisand, H. Mazarguil, C. Mollereau, and J. C. Meunier. (1997) Recognition and activation of the opioid receptor-like ORL 1 receptor by nociceptin, nociceptin analogs and opioids. European Journal of Pharmacology 321, 97–103.
Guerrini R., G. Calo, A. Rizzi, C. Bianchi, L. H. Lazarus, S. Salvadori, P. A. Temussi, and D. Regoli. (1997) Address and message sequences for the nociceptin receptor: A structure-activity study of nociceptin-(1-13)-peptide amide. Journal of Medicinal Chemistry 40, 1789–1793.
Anton B., J. Fein, T. To, X. Li, L. Silberstein, and C. J. Evans. (1996) Immunohistochemical localization of ORL-1 in the central nervous system of the rat. J. Comp. Neurol. 368, 229–251.
Chen Y., Y. Fan, J. Liu, A. Mestek, M. Tian, C. A. Kozak, and L. Yu. (1994) Molecular cloning, tissue distribution and chromosomal localization of a novel member of the opioid receptor gene family. FEBS Lett. 347, 279–283.
Fukuda K., S. Kato, K. Mori, M. Nishi, H. Takeshima, N. Iwabe, T. Miyata, T. Houtani, and T. Sugimoto. (1994) cDNA cloning and regional distribution of a novel member of the opioid receptor family. FEBS Lett. 343, 42–46.
Riedl M., S. Shuster, L. Vulchanova, J. Wang, H. H. Loh, and R. Elde. (1996) Orphanin FQ/nociceptin-immunoreactive nerve fibers parallel those containing endogenous opioids in rat spinal cord. Neuroreport 7, 1369–1372.
Wick M. J., S. R. Minnerath, X. Lin, R. Elde, P. Y. Law, and H. H. Loh. (1994) Isolation of a novel cDNA encoding a putative membrane receptor with high homology to the cloned mu, delta, and kappa opioid receptors. Brain Res. Mol. Brain Res. 27, 37–44.
Lee K., J. R. Nicholson, and A. T. McKnight. (1997) Nociceptin hyperpolarises neurones in the rat ventromedial hypothalamus. Neuroscience Letters 239, 37–40.
Martini L., D. Dondi, P. Limonta, R. Maggi, and F. Piva. (1989) Modulation by sex steroids of brain opioid receptors: implications for the control of gonadotropins and prolactin secretion. J. Steroid Biochem. 33, 673–681.
Mateo A. R., M. Hijazi, and R. P. Hammer, Jr. (1992) Dynamic patterns of medial preoptic mu-opiate receptor regulation by gonadal steroid hormones. Neuroendocrinology 55, 51–58.
Thom B., B. J. Canny, M. Cowley, P. J. Wright, and I. J. Clarke. (1996) changes in the binding characteristics of the μ, δ, and κ subtypes of the opioid receptor in the hypothalamus of the normal cyclic ewe and in the ovariectomized ewe following treatment with ovarian steroids. J. Endocrinol. 149, 509–518.
Weiland N. G. and P. M. Wise. (1990) Estrogen and progesterone regulate opiate receptor densities in multiple brain regions. Endocrinology 126, 804–808.
Wilkinson M., J. R. Brawer, and D. A. Wilkinson. (1985) Gonadal steroid-induced modification of opiate binding sites in anterior hypothalamus of female rats. Biol. Reprod. 32, 501–506.
Zhou L. and R. P. Hammer, Jr. (1995) Gonadal steroid hormones upregulate medial preoptic mu-opioid receptors in the rat. Eur. J. Pharmacol. 278, 271–274.
Piva F., P. Limonta, D. Dondi, F. Pimpinelli, L. Martini, and R. Maggi. (1995) Effects of steroids on the brain opioid system. J. Steroid Biochem. Mol. Biol. 53, 343–348.
Maggi R., D. Dondi, G. E. Rovati, L. Martini, F. Piva, and P. Limonta. (1993) Binding Characteristics of Hypothalamic Mu Opioid Receptors Throughout the Estrous Cycle in the Rat. Neuroendocrinology 58, 366–372.
Micevych P.E., V. Chaban, A. Quesada, and K. Sinchak. (2002) Estrogen modulates CCK—Opioid interactions in the nervous system. Pharmacology and Toxicology 91, 387–397.
Allen B. J., S. D. Rogers, J. R. Ghilardi, P. M. Menning, M. A. Kuskowski, A. I. Basbaum, D. A. Simone, and P. W. Mantyh. (1997) Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: Imaging peptide action in vivo. J. Neurosci. 17, 5921–5927.
Grady E. F., A. M. Garland, P. D. Gamp, M. Lovett, D. G. Payan, and N. W. Bunnett. (1995) Delineation of the endocytic pathway of substance P and its seven-transmembrane domain NK1 receptor. Mol. Biol. Cell. 6, 509–524.
Hoxie J. A., M. Ahuja, E. Belmonte, S. Pizarro, R. Parton, and L. F. Brass. (1993) Internalization and recycling of activated thrombin receptors. J. Biol. Chem. 268, 13,756–13,763.
Parker E. M., P. Swigart, M. H. Nunnally, J. P. Perkins, and E. M. Ross. (1995) Carboxyl-terminal domains in the avian beta 1-adrenergic receptor that regulate agonist-promoted endocytosis [published erratum appears in J. Biol. Chem. 1995 Apr 28;270(17):10358]. J. Biol. Chem. 270, 6482–6487.
von Zastrow M. and B. K. Kobilka. (1992) Lig-and-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors. J. Biol. Chem. 267, 3530–3538.
Caron M. G. and R. J. Lefkowitz. (1993) Cate-cholamine receptors: Structure, function, and regulation. Recent Prog. Horm. Res. 48, 277–290.
Mantyh P. W., C. J. Allen, J. R. Ghilardi, S. D. Rogers, C. R. Mantyh, H. Liu, A. I. Basbaum, S. R. Vigna, and J. E. Maggio. (1995) Rapid endocytosis of a G protein-coupled receptor: Substance P evoked internalization of its receptor in the rat striatum in vivo. Proc. Natl. Acad. Sci. USA 92, 2622–2626.
Mantyh P. W., E. DeMaster, A. Malhotra, J. R. Ghilardi, S. D. Rogers, C. R. Mantyh, H. Liu, A. I. Basbaum, S. R. Vigna, J. E. Maggio, et al. (1995) Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation. Science 268, 1629–1632.
Sternini C., M. Spann, B. Anton, D. E. Keith, Jr., N. W. Bunnett, M. von Zastrow, C. Evans, and N. C. Brecha. (1996) Agonist-selective endocytosis of mu opioid receptor by neurons in vivo. Proc. Natl. Acad. Sci. USA 93, 9241–9246.
von Zastrow M., D. Keith, P. Zaki, and C. Evans. (1994) Intracellular trafficking of epitope-tagged opioid receptors different effects of morphine and enkephalin. Regul. Pept. 54, 315–316.
Law P. Y., D. S. Hom, and H. H. Loh. (1982) Loss of opiate receptor activity in neuroblastoma X glioma NG108-15 hybrid cells after chronic opiate treatment. A multiple-step process. Molecular Pharmacology 22, 1–4.
Law P. Y., D. S. Hom, and H. H. Loh. (1984) Down-regulation of opiate receptor in neuroblastoma x glioma NG108-15 hybrid cells. Chloroquine promotes accumulation of tritiated enkephalin in the lysosomes. Journal of Biological Chemistry 259, 4096–4104.
Sharma S. K., W. A. Klee, and M. Nirenberg. (1977) Opiate-dependent modulation of adenylate cyclase. Proc. Natl. Acad. Sci. USA 74, 3365–3369.
Mestek A., J. H. Hurley, L. S. Bye, A. D. Campbell, Y. Chen, M. Tian, J. Liu, H. Schulman, and L. Yu. (1995) The human mu opioid receptor. Journal of Neuroscience 15, 2396–2406.
Louie A. K., J. N. Zhan, P. Y. Law, and H. H. Loh. (1988) Modification of opioid receptor activity by acid phosphatase in neuroblastoma x glioma NG108-15 hybrid cells. Biochemical and Biophysical Research Communications 152, 1369–1375.
Arden J. R., V. Segredo, Z. Wang, J. Lameh, and W. Sadaee. (1995) Phosphorylation and agonist-specific intracellular trafficking of an epitope-tagged mu-opioid receptor expressed in HEK 293 cells. Journal of Neurochemistry 65, 1636–1645.
Keith D. E., S. R. Murray, P. A. Zaki, P. C. Chu, D. V. Lissin, L. Kang, C. J. Evans, and M. von Zastrow. (1996) Morphine activates opioid receptors without causing their rapid internalization. J. Bio. Chem. 271, 19,021–19,024.
von Zastrow M., D. E. Keith, Jr., and C. J. Evans. (1993) Agonist-induced state of the delta-opioid receptor that discriminates between opioid peptides and opiate alkaloids. Mol. Pharmacol. 44, 166–172.
Eckersell C. B. and P. E. Micevych (submitted) Distribution of μ- and δ-opioid receptors with respect to CCK immunoreactivity in the hypothalamus and limbic system.
Sherman M. R. and S. C. Diaz. (1977) Meroreceptor formation from a larger subcomponent of the oviduct progesterone receptor. Ann. NY Acad. Sci. 286, 81–86.
Olive F. M., J. C. Evans, P. E. Micevych, and N. T. Maidment. (1997) Pre- vs Postsynaptic localization of mu and delta opioid receptors in the striatopallidal pathway. J. Neurosci. 17, 7471–7479.
Arvidsson U., M. Riedl, S. Chakrabarti, J. H. Lee, A. H. Nakano, R. J. Dado, H. H. Loh, P. Y. Law, M. W. Wessendorf, and R. Elde. (1995) Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord. J. Neurosci. 15, 3328–3341.
Elde R., U. Arvidsson, M. Riedl, L. Vulchanova, J. H. Lee, R. Dado, A. Nakano, S. Chakrabarti, X. Zhang, H. H. Loh, et al. (1995) Distribution of neuropeptide receptors. New views of peptidergic neurotransmission made possible by antibodies to opioid receptors. Ann. NY Acad. Sci. 757, 390–404.
Cheng P. Y., L. Y. Liu-Chen, C. Chen, and V. M. Pickel. (1996) Immunolabeling of Mu opioid receptors in the rat nucleus of the solitary tract: extrasynaptic plasmalemmal localization and association with Leu5-enkephalin. J. Comp. Neurol. 371, 522–536.
Svingos A. L., A. Moriwaki, J. B. Wang, G. R. Uhl, and V. M. Pickel. (1996) Ultrastructural immunocytochemical localization of mu-opioid receptors rat nucleus accumbens: extrasynaptic plasmalemmal distribution and association with Leu5-enkephalin. J. Neurosci. 16, 4162–4173.
Wang X. M., K. M. Zhang, and S. S. Mokha. (1996) Nociceptin (orphanin FQ), an endogenous ligand for the ORL1 (opioid-receptor-like1) receptor; modulates responses of trigeminal neurons evoked by excitatory amino acids and somatosensory stimuli. J. Neurophysiol. 76, 3568–3572.
Van Bockstaele E. J., E. E. Colago, A. Moriwaki, and G. R. Uhl. (1996) Mu-opioid receptor is located on the plasma membrane of dendrites that receive asymmetric synapses from axon terminals containing leucine-enkephalin in the rat nucleus locus coeruleus. J. Comp. Neurol. 376, 65–74.
Keith D. E., B. Anton, S. R. Murray, P. A. Zaki, P. C. Chu, D. V. Lissin, G. Monteillet-Agius, P. L. Stewart, C. J. Evans, and M. von Zastrow. (1998) mu-Opioid receptor internalization: opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain. Molecular Pharmacology 53, 377–384.
McConalogue, K., E. F. Grady, J. Minnis, B. Balestra, M. Tonini, N. C. Brecha, N. W. Bunnett, and C. Sternini. (1999) Activation and internalization of the mu-opioid receptor by the newly discovered endogenous agonists, endomorphin-1 and endomorphin-2. Neuroscience 90, 1051–1059.
Keith D., S. Murray, P. Zaki, P. Chu, D. Lisson, L. Kang, J. Aimi, C. Evans, and M. von Zastrow. (1995) Rapid endocytosis of opioid receptors: Differential regulation by opioid peptide and morphine. Soc. Neurosci. Abstr. 21, 1353.
Dournaud P., H. Boudin, A. Schonbrunn, G. S. Tannenbaum, and A. Beaudet. (1998) Interrelationships between somatostatin sst2A receptors and somatostatin-containing axons in rat brain: Evidence for regulation of cell surface receptors by endogenous somatostatin. Journal of Neuroscience 18, 1056–1071.
Jacobson W. and S. P. Kalra. (1989) Decreases in mediobasal hypothalamic and preoptic area opioid ([3H]naloxone) binding are associated with the progesterone-induced luteinizing hormone surge. Endocrinology 124, 199–206.
Zhou, Y., Y.-H. Sun, Z.-W. Zhang, and J.-S. Han. (1993) Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCK-B receptor antagonist L-365,260 in rat spinal cord. Europ. J. Pharmoc. 234, 147–154.
Collin E., S. Bourgoin, S. Mantelet, M. Hamon, and F. Cesselin. (1992) Feedback inhibition of met-enkephalin release from the rat spinal cord in vivo. Synapse 11, 76–84.
Pierce T. L. and M. W. Wessendorf. (2000) Immunocytochemical mapping of endomorphin-2-immunoreactivity in rat brain. Journal of Chemical Neuroanatomy 18, 181–207.
Shughrue P. J., M. V. Lane, P. J. Scrimo, and I. Merchenthaler. (1998) Comparative distribution of estrogen receptor-alpha (ER-alpha) and beta (ER-beta) mRNA in the rat pituitary, gonad, and reproductive tract. Steroids 63, 498–504.
Clark J. T., P. S. Kalra, and S. P. Kalra. (1985) Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. Endocrinology 117, 2435–2442.
Mills R. H., R. K. Sohn, and P. E. Micevych. (2001) Effects of neuropeptide Y on steroid activation of m-opioid receptor and neuropeptide Y-Y1 receptor in the hypothalamus in female rats. Society for Behavioral Neuroendocrinology 39, 339–340.
Webb P., G. N. Lopez, R. M. Uht, and P. J. Kushner. (1995) Tamoxifen activation of the estrogen. Molecular Endocrinology 9, 443–456.
Gu Q., K. S. Korach, and R. L. Moss. (1999) Rapid action of 17beta-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors. Endocrinology 140, 660–666.
Lubahn D. B., J. S. Moyer, T. S. Golding, J. F. Couse, K. S. Korach, and O. Smithies. (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. USA 90, 11,162–11,166.
Korach K. S. (1994) Insights from the study of animals lacking functional estrogen receptor. Science 266, 1524–1527.
Kuiper G., E. Enmark, M. Pelto-Huikko, S. Nilsson, and J.-A. Gustafsson. (1996) Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. 93, 5925–5930.
Kuiper G. G., P. J. Shughrue, I. Merchenthaler, and J. A. Gustafsson. (1998) The estrogen receptor beta subtype: a novel mediator of estrogen action in neuroendocrine systems. Frontiers in Neuroendocrinology 19, 253–286.
Kuiper G. G., B. Carlsson, K. Grandien, E. Enmark, J. Heaggblad, S. Nilsson, and J. A. Gustafsson. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138, 863–870.
Rissman E. F., S. R. Wersinger, J. A. Taylor, and D. B. Lubahn. (1997) Estrogen receptor function as revealed by knockout studies: neuroendocrine and behavioral aspects. Hormones and Behavior 31, 232–243.
Tremblay G. B., A. Tremblay, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, F. Labrie, and V. Giguere. (1997) Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta. Mol. Endocrinol. 11, 353–365.
Mosselman S., J. Polman, and R. Dijkema. (1996) ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392, 49–53.
Micevych P. E., E. F. Rissman, and K. Sinchak. (2003) Estrogen receptor-α is required for estrogen-induced μ-opioid receptor internalization. J. Neurosci. Res. 71, 802–810.
Fedynyshyn J. P. and N. M. Lee. (1989) Mutype opioid receptors in rat periaqueductal gray-enriched P2 membrane are coupled to guanine nucleotide binding proteins. Brain Res. 476, 102–109.
Selley D. E. and J. M. Bidlack. (1992) Effects of Beta-Endorphin on Mu and Delta Opioid Receptor-Coupled G-Protein Activity—Low-Km GTPase Studies. Journal of Pharmacology and Experimental Therapeutics 263, 99–104.
Chakrabarti S., P. L. Prather, L. Yu, P. Y. Law, and H. H. Loh. (1995) Expression of the mu-opioid receptor in CHO cells—Ability of mu-opioid ligands to promote alpha-azidoanilido [P-32]GTP labeling of multiple G protein alpha subunits. J. Neurochem. 64, 2534–2543.
Frey E. A. and J. W. Kebabian. (1984) A mu-opiate receptor in 7315c tumor tissue mediates inhibition of immunoreactive prolactin release and adenylate cyclase activity. Endocrinology 115, 1797–1804.
Yu V. C. and W. Sadee. (1988) Efficacy and tolerance of narcotic analgesics at the mu opioid receptor in differentiated human neuroblastoma cells. J. Pharmacol. Exp. Ther. 245, 350–355.
Childers S. R. (1991) Opioid receptor-coupled second messenger systems. Life Sci. 48, 1991–2003.
Aghajanian G. K. and Y. Y. Wang. (1986) Pertussis toxin blocks the outward currents evoked by opiate and alpha 2-agonists in locus coeruleus neurons. Brain Res. 371, 390–394.
North R. A., J. T. Williams, A. Surprenant, and M. J. Christie. (1987) Mu and delta receptors belong to a family of receptors that are coupled to potassium channels. Proc. Natl. Acad. Sci. USA 84, 5487–5491.
Moises H. C., K. I. Rusin, and R. L. Macdonald. (1994) Mu-and kappa-opioid receptors selectively reduce the same transient components of high-threshold calcium current in rat dorsal root ganglion sensory neurons. J. Neurosci. 14, 5903–5916.
Moises H. C., K. I. Rusin, and R. L. Macdonald. (1994) mu-Opioid receptor-mediated reduction of neuronal calcium current occurs via a G(o)-type GTP-binding protein. J. Neurosci. 14, 3842–3851.
Rhim H. and R. J. Miller. (1994) Opioid receptors modulate diverse types of calcium channels in the nucleus tractus solitarius of the rat. J. Neurosci. 14, 7608–7615.
Kelly M. J. and E. R. Levin. (2001) Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol. Metab. 12, 152–156.
Kelly M. J., A. H. Lagrange, E. J. Wagner, and O. K. Ronnekleiv. (1999) Rapid effects of estrogen to modulate G protein-coupled receptors via activation of protein kinase A and protein kinase C pathways. Steroids 64, 64–75.
Russell K. S., M. P. Haynes, D. Sinha, E. Clerisme, and J. R. Bender. (2000) Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc. Nat. Acad. Sci. USA 97, 5930–5935.
Pietras R. J., I. Nemere, and C. M. Szego. (2001) Steroid hormone receptors in target cell membranes. Endocrine 14, 417–427.
Pietras P. J. and C. M. Szego. (1999) Cell membrane estrogen receptors resurface. Nat. Med. 5, 1330.
Pietras R. J. and C. M. Szego. (1977) Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature 265, 69–72.
Sim L. J. and S. R. Childers. (1997) Anatomical distribution of mu, delta, and kappa opioid- and nociceptin/orphanin FQ stimulated [35S]Guanylyl-5′-O-(γ-thio)-triphosphate binding in guinea pig brain. J. Comp. Neurol. 386, 562–572.
Sim L. J., Q. Liu, S. R. Childers, and D. E. Selley. (1998) Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors. Journal of Neurochemistry 70, 1567–1576.
Sim L. J., D. E. Selley, and S. R. Childers. (1995) In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5′-[gamma-[35S]thio]-triphosphate binding. Proc. Nat. Acad. Sci. USA 92, 7242–7246.
Sim L. J., D. E. Selley, S. I. Dworkin, and S. R. Childers. (1996) Effects of chronic morphine administration on μ-opioid receptor-stimulated [35S]GTPγS autoradiography in rat brain. J. Neurosci. 16, 2684–2692.
Sim L. J., D. E. Selley, R. Xiao, and S. R. Childers. (1996) Differences in G-protein activation by μ- and δ-opioid, and cannabinoid, receptors in rat striatum. Europ. J. Pharmacol. 307, 97–105.
Selley D. E., L. J. Sim, R. Y. Xiao, Q. X. Liu, and S. R. Childers. (1997) mu-Opioid receptor-stimulated guanosine-5′-O-(γ-thio)-triphosphate binding in rat thalamus and cultured cell lines: Signal transduction mechanisms underlying agonist efficacy. Mol. Pharmacol. 51, 87–96.
Cunningham M. J., Y. Fang, D. E. Selley, and M. J. Kelly. (1998) mu-Opioid agonist-stimulated [35S]GTPγS binding in guinea pig hypothalamus: effects of estrogen. Brain Res. 791, 341–346.
Bueno J. and D. W. Pfaff. (1976) Single unit recording in hypothalamus and preoptic area of estrogen-treated and untreated ovariectomized female rats. Brain Res. 101, 67–78.
Lincoln D. W. (1967) Unit activity in the hypothalamus, septum and preoptic area of the rat: characteristics of spontaneous activity and the effect of oestrogen. J. Endocrinol. 37, 177–189.
Sinchak K., V. Yu, and P. E. Micevych. (1998) Progesterone induces internalization of ORl-1 in the ventromedial nucleus of the hypothalamus in estrogen primed female rats but does not increase the area of immunoreactivity. Soc. Neurosci. Abstr. 24, 1011.
Neal C. R., A. Mansour, R. Reinscheid, H. P. Nothacker, O. Civelli, H. Akil, and S. J. Watson. (1999) Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: Comparison of ORL1 receptor mRNA expression with I-125-[(14)Tyr]-orphanin FQ binding. J. Comp. Neurol. 412, 563–605.
Sinchak K., R. Khavari, D. Katzman, and P. E. Micevych. (1999) Sexual receptivity is associated with a reduction in internalization of mu-opioid receptors in the medial preoptic nucleus in cycling and steroid primed ovariectomized rats. Soc. Neurosci. Abst. 25, 1705.
Popper P., C. A. Priest, and P. E. Micevych. (1996) Regulation of cholecystokinin receptors in the ventromedial nucleus of the hypothalamus: Sex steroid hormone regulation. Brain Res. 715, 335–339.
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Sinchak, K., Micevych, P. Visualizing activation of opioid circuits by internalization of G protein-coupled receptors. Mol Neurobiol 27, 197–222 (2003). https://doi.org/10.1385/MN:27:2:197
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DOI: https://doi.org/10.1385/MN:27:2:197