Progesterone Receptor Expression in the Developing Mesocortical Dopamine Pathway: Importance for Complex Cognitive Behavior in Adulthood (original) (raw)
Article navigation
Review Articles| June 10 2015
aDepartment of Psychology, and
bCenter for Neuroscience Research, University at Albany, SUNY, Albany, N.Y., and
cBehavioral Neuroscience Division, Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, Ill., USA
Search for other works by this author on:
aDepartment of Psychology, and
bCenter for Neuroscience Research, University at Albany, SUNY, Albany, N.Y., and
Search for other works by this author on:
Neuroendocrinology (2016) 103 (3-4): 207–222.
Abstract
Background: Numerous psychiatric and behavioral disorders such as autism, attention deficit disorder and schizophrenia may involve disruptions in the development of the mesocortical dopamine pathway, consisting of dopaminergic projections from the midbrain ventral tegmental area (VTA) to the medial prefrontal cortex (mPFC). Nuclear steroid hormone receptors are powerful transcription factors and can profoundly and permanently alter fundamental processes of neural development. Nuclear progesterone receptor (PR) is transiently expressed in both the VTA and the PFC of rodents during perinatal life, suggesting that PR may regulate the normal development of this important behavioral circuit. Methods and Results: Here, we demonstrate that virtually all PR-immunoreactive (PR-ir) cells in the VTA also express tyrosine hydroxylase immunoreactivity (TH-ir). In addition, retrograde tract tracing reveals that many PR-ir cells in the VTA project to the mPFC. Administration of a PR antagonist to rats during the neonatal period decreased TH-ir fiber density in the prelimbic mPFC of juveniles (postnatal day 25) and decreased levels of TH-ir in the VTA of adults. Neonatal treatment with a PR antagonist impaired adult performance on a passive inhibitory avoidance task and an attentional set-shifting task, measures of behavioral inhibition/impulsivity and cognitive flexibility, respectively. TH-ir levels in the VTA were reduced and cognitive flexibility was impaired in PR knockout mice as well. Conclusions: These findings provide novel insights into a potential role for PR in the developmental etiology of behavioral disorders that involve impairments in complex cognitive behaviors and have implications for the use of synthetic progestins in humans during critical neurodevelopmental periods.
References
Goto Y, Grace AA: Alterations in medial prefrontal cortical activity and plasticity in rats with disruptions of cortical development. Biol Psychiatry 2006;60:1259-1267.
Floresco SB, Magyar O: Mesocortical dopamine modulation of executive functions: beyond working memory. Psychopharmacology 2006;188:567-585.
Sullivan RM, Brake WG: What the rodent prefrontal cortex can teach us about attention deficit/hyperactivity disorder: the critical role of early developmental events on prefrontal function. Behav Brain Res 2003;146:43-55.
Viggiano D, Vallone D, Ruocco LA, Sadile AG: Behavioural, pharmacological, morpho-functional molecular studies reveal a hyperfunctioning mesocortical dopamine system in an animal model of attention deficit and hyperactivity disorder. Neurosci Biobehav Rev 2003;27:683-689.
Arnsten AF, Li BM: Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 2005;57:1377-1384.
Brennan AR, Arnsten AFT: Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function. Ann NY Acad Sci 2008;1129:236-245.
Prince J: Catecholamine dysfunction in attention deficit-hyperactivity disorder: an update. J Clin Psychopharmacol 2008;28(suppl 2):S39-S45.
Quadros PS, Pfau JL, Wagner CK: Distribution of progesterone receptor immunoreactivity in the fetal and neonatal rat forebrain. J Comp Neurol 2007;504:42-56.
Quadros PS, Schlueter LJ, Wagner CK: Distribution of progesterone receptor immunoreactivity in the midbrain and hindbrain of postnatal rats. Dev Neurobiol 2008;68:1378-1390.
Lopez V, Wagner CK: Progestin receptor is transiently expressed perinatally in neurons of the rat isocortex. J Comp Neurol 2009;512:124-139.
Jahagirdar V, Wagner CK: Ontogeny of progesterone receptor expression in the subplate of fetal and neonatal rat cortex. Cereb Cortex 2010;20:1046-1052.
Beyer C, Damm N, Brito V, Kuppers E: Developmental expression of progesterone receptor isoforms in the mouse midbrain. Dev Neurosci 2002;13:877-880.
De Brabander JM, Kramers JK, Uylings HBM: Layer-specific dendritic regression of pyramidal cells with aging in the human prefrontal cortex. Eur J Neurosci 1998;10:1261-1269.
Petanjek Z, Judas M, Kostovic I, Uylings HBM: Lifespan alterations of basal dendritic trees of pyramidal neurons in the human prefrontal cortex: a layer-specific pattern. Cereb Cortex 2008;18:915-929.
Ernst M, Fudge JL: A developmental neurobiological model of motivated behavior: anatomy, connectivity and ontogeny of the triadic nodes. Neurosci Biobehav Rev 2009;33:367-382.
Diaz NF, Guerra-Arraiza C, Diaz-Martinez NE, Salazar P, Molina-Hernandez A, Camacho-Arroyo I, Velasco I: Changes in the content of estrogen and progesterone receptors during differentiation of mouse embryonic stem cells to dopamine neurons. Brain Res Bull 2007;73:75-80.
Muneoka K, Kuwagata M, Ogawa T, Shioda S: Sex-specific effects of early neonatal progesterone treatment on dopamine and serotonin metabolism in rat striatum and frontal cortex. Life Sci 2010;87:738-742.
Lydon J, DeMayo F, Funk C, Mani S, Hughes A, Montgomery C, Shyamala G, Conneely OM, O'Malley BW: Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev 1995;9:2266-2278.
Lonstein JS, Quadros PS, Wagner CK: Effects of neonatal RU486 on adult sexual, parental and fearful behaviors in rats. Behav Neurosci 2001;115:58-70.
Quadros PS, Lopez V, De Vries GJ, Chung WC, Wagner CK: Progesterone receptors and the sexual differentiation of the medial preoptic nucleus. J Neurobiol 2002;51:24-32.
Traish AM, Wotiz HH: Monoclonal and polyclonal antibodies to human progesterone receptor peptide-(533-547) recognize a specific site in unactivated (8S) and activated (4S) progesterone receptor and distinguish between intact and proteolyzed receptors. Endocrinology 1990;127:1167-1175.
Tetel MJ, Jung S, Carbajo P, Ladtkow T, Skafar DF, Edwards DP: Hinge and amino-terminal sequences contribute to solution dimerization of human progesterone receptor. Mol Endocrinol 1997;11:1114-1128.
Karatsoreos IN, Bhagat S, Bloss EB, Morrison JH, McEwen BS: Disruption of circadian clocks has ramifications for metabolism, brain and behavior. Proc Natl Acad Sci USA 2011;108:1657-1662.
Gonzales KL, Tetel MJ, Wagner CK: Estrogen receptor (ER) β modulates ERα responses to estrogens in the developing rat ventromedial nucleus of the hypothalamus. Endocrinology 2008;149:4615-4621.
Heller A, Hutchens JO, Kirby ML, Karapas F, Fernandez C: Stereotaxic electrode placement in the neonatal rat. J Neurosci Methods 1979;1:41-76.
Kalsbeek A, Voorn P, Buijs RM, Pool CW, Uylings HB: Development of the dopaminergic innervation in the prefrontal cortex of the rat. J Comp Neurol 1988;269:58-72.
Lieb K, Anderson C, Lazarov N, Zienecker R, Urban I, Reisert I, Pilgrim C: Pre- and postnatal development of dopaminegic neuron numbers in the male and female mouse midbrain. Dev Brain Res 1996;94:37-43.
Park M, Kitahama K, Geffard M, Maeda T: Postnatal development of the dopaminergic neurons in the rat mesencephalon. Brain Dev 2000;22:S38-S44.
Prakash N, Wurst W: Development of dopaminergic neurons in the mammalian brain. Cell Mol Life Sci 2006;63:197-206.
Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates. San Diego, Academic Press, 1998.
Naneix F, Marchand AR, Di Scala D, Pape JR, Coutureau E: A role for medial prefrontal dopaminergic innervation in instrumental conditioning. J Neurosci 2009;29:6599-6606.
Van Eden CG, Uylings HBM: Cytoarchitectonic development of the prefrontal cortex in the rat. J Comp Neurol 1985;241:253-267.
Kritzer MF: Long term gonadectomy affects the density of tyrosine hydroxylase but not dopamine-β-hydroxylase, choline acetyltransferase or serotonin immunoreactive axons in the medial prefrontal cortices of adult male rats. Cereb Cortex 2003;13:282-296.
Roozendaal B, McReynolds JR, Van der Zee EA, Lee S, McGaugh JL, McIntyre CK: Glucocorticoid effects on memory consolidation depend on functional interactions between the medial prefrontal cortex and basolateral amygdala. J Neurosci 2009;29:14299-14308.
McReynolds JR, Holloway-Erickson CM, Parmar TU, McIntyre CK: Corticosterone-induced enhancement of memory and synaptic Arc protein in the medial prefrontal cortex. Neurobiol Learn Mem 2014;112:148-157.
Yang FC, Liang KC: Interactions of the dorsal hippocampus, medial prefrontal cortex and nucleus accumbens in formation of fear memory: difference in inhibitory avoidance learning and contextual fear conditioning. Neurobiol Learn Mem 2014;112:186-194.
Stefani MR, Moghaddam B: Rule learning and reward contingency are associated with dissociable patterns of dopamine activation in the rat prefrontal cortex, nucleus accumbens and dorsal striatum. J Neurosci 2006;26:8810-8818.
Ragozzino ME, Detrick S, Kesner RP: Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning. J Neurosci 1999;19:4585-4594.
Birrell JM, Brown VJ: Medial prefrontal cortex mediates perceptual attentional set-shifting in the rat. J Neurosci 2000;20:4320-4324.
Ragozzino ME, Hassert KJ, Minniti N, Kiang C: The contribution of the rat prelimbic-infralimbic areas to different forms of task switching. Behav Neurosci 2003;117:1054-1065.
Floresco SB, Block AE, Tse MTL: Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure. Behav Brain Res 2008;190:85-96.
Rich EL, Shapiro M: Rat prefrontal cortical neurons selectively code strategy switches. J Neurosci 2009;29:7208-7219.
Jahng JW, Ryu V, Yoo SB, Noh SJ, Kim JY, Lee JH: Mesolimbic dopaminergic activity responding to acute stress is blunted in adolescent rats that experienced neonatal maternal separation. Neuroscience 2010;171:144-152.
Kritzer MF: Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area, substantia nigra and retrorubral fields in the rat. J Comp Neurol 1997;379:247-260.
Creutz LM, Kritzer MF: Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats. J Comp Neurol 2004;476:348-362.
Kritzer MF, Creutz LM: Region and sex differences in constituent dopamine neurons and immunoreactivity for intracellular estrogen and androgen receptors in mesocortical projections in rats. J Neurosci 2008;28:9525-9535.
Cruz G, Riquelme R, Espinosa P, Jara P, Dagino-Subiabre A, Renard GM, Sotomayor-Zarate R: Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat. Horm Metab Res 2014;46:322-327.
Jensik PJ, Arbogast LA: Differential and interactive effects of ligand-bound progesterone receptor A and B isoforms on tyrosine hydroxylase promoter activity. J Neuroendocrinol 2011;23:915-925.
Willing J, Wagner CK: Sensorimotor development in neonatal progesterone receptor knockout mice. Dev Neurobiol 2014;74:16-24.
Segal M, Murphy D: Estradiol induces formation of dendritic spines in hippocampal neurons: functional correlates. Horm Behav 2001;40:156-159.
Yuste R, Bonhoeffer T: Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 2001;24:1071-1089.
Murphy DD, Segal M: Progesterone prevents estradiol-induced dendritic spine formation in cultured hippocampal neurons. Neuroendocrinology 2000;72:133-143.
Woolley CS: Effects of oestradiol on hippocampal circuitry. Novartis Found Symp 2000;230:173-180, discussion 181-187.
Mong JA, Roberts RC, Kelly JJ, McCarthy MM: Gonadal steroids reduce the density of axospinous synapses in the developing rat arcuate nucleus: an electron microscopy analysis. J Comp Neurol 2001;432:259-267.
Sakamoto H, Ukena K, Tsutsui K: Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis. J Neurosci 2001;21:6221-6232.
Isgor C, Sengelaub DR: Effects of neonatal gonadal steroids on adult CA3 pyramidal neuron dendritic morphology and spatial memory in rats. J Neurobiol 2003;55:179-190.
Sakamoto H, Ukena K, Tsutsui K: Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats. Neurosci Lett 2002;322:111-115.
Sakamoto H, Mezaki Y, Shikimi H, Ukena K, Tsutsui K: Dendritic growth and spine formation in response to estrogen in the developing Purkinje cell. Endocrinology 2003;144:4466-4477.
Menzies KD, Drysdale DB, Waite PM: Effects of prenatal progesterone on the development of pyramidal cells in rat cerebral cortex. Exp Neurol 1982;77:654-667.
Pluchino N, Russo M, Santoro AN, Litta P, Cela V, Genazzani AR: Steroid hormones and BDNF. Neuroscience 2013;239:271-279.
Jodhka PK, Kaur P, Underwood W, Lydon JP, Singh M: The differences in neuroprotective efficacy of progesterone and medroxyprogesterone acetate correlate with their effects on brain-derived neurotrophic factor expression. Endocrinology 2009;150:3162-3168.
Mello E, Souza T, Vianna MR, Rodrigues C, Quevedo J, Moleta BA, Izquierdo I: Involvement of the medial precentral prefrontal cortex in memory consolidation for inhibitory avoidance learning in rats. Pharmacol Biochem Behav 2000;66:615-622.
Kritzer MF, Brewer A, Montalmant F, Davenport M, Robinson JK: Effects of gonadectomy and hormone replacement on operant tasks measuring prefrontal cortical function in adult male rats. Horm Behav 2007;51:183-194.
Ordya NE, Galeeva AY, Pivina SG: Expression of glucocorticoid receptor in the brain of rats during postnatal ontogeny. Bull Exp Biol Med 2008;146:176-179.
Pryce CR: Postnatal ontogeny of expression of the corticosteroid receptor genes in mammalian brains: inter-species and intra-species differences. Brain Res Rev 2008;57:596-605.
Schmouder VM, Prescott GM, Franco A, Fan-Havard P: The rebirth of progesterone in the prevention of preterm labor. Ann Pharmacother 2013;47:527-536.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
Sign in
Digital Version
Pay-Per-View Access
$45.00
1 Karger Article Bundle Token
$170
Rental
This article is also available for rental through DeepDyve. 