Advanced search
Publication Cover
Future Medicinal Chemistry Volume 1, 2009 - Issue 7
Submit an article Journal homepage
49
Views
0
CrossRef citations to date
0
Altmetric
Perspective

Progestogens Influence Cognitive Processes in Aging

Cheryl A Frye1 Department of Psychology, The University at Albany, SUNY, Life Sciences Research Building 01058, 1400 Washington Avenue, Albany, NY12222, USACorrespondence[email protected]
View further author information
Pages 1215-1231 | Published online: 21 Oct 2009

Bibliography

  • Rhodes ME , FryeCA. Attenuating 5α-pregnane-3α-ol-20-one formation in the hippocampus of female rats increases pentylenetetrazole-induced seizures.Epilepsy Behav.6(2), 140–146 (2005).
  • Rhodes ME , FryeCA. Actions at GABAA receptors in the hippocampus may mediate some of progestins’ anti-seizure effects. Epilepsy Behav.6, 320–327 (2005).
  • Rhodes ME , FryeCA. Progestins in the hippocampus of female rats have anti-seizure effects in a pentylenetetrazole seizure model.Epilepsia45, 1531–1538 (2004).
  • Iswari S , ColasAE, KaravolasHJ. Binding of 5 α-dihydroprogesterone and other progestins to female rat anterior pituitary nuclear extracts.Steroids47(2–3), 189–203 (1986).
  • Gee KW , BolgerMB, BrintonRE, CoiriniH, McEwenBS. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action.J. Pharmacol. Exp. Ther.246(2), 803–812 (1988).
  • Sheridan PJ . Autoradiographic localization of steroid receptors in the brain.Clin. Neuropharmacol.7(4), 281–295 (1984).
  • Shughrue PJ , MerchenthalerI. Distribution of estrogen receptor β immunoreactivity in the rat central nervous system.J. Comp. Neurol.436(1), 64–81 (2001).
  • Kellogg CK , KenjarskiTP, PlegerGL, FryeCA. Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids.Brain Res.1067(1), 115–125 (2006).
  • Walf AA , KoonceCJ, FryeCA. Estradiol or diarylpropionitrile administration to wild type, but not estrogen receptor β knockout, mice enhances performance in the object recognition and object placement tasks.Neurobiol. Learn Mem.89(4), 513–521 (2008).
  • Rhodes ME , FryeCA. Progestins in the hippocampus of female rats have antiseizure effects in a pentylenetetrazole seizure model.Epilepsia45(12), 1531–1538 (2004).
  • Edwards HE , EppsT, CarlenPL, MacLuskyJN. Progestin receptors mediate progesterone suppression of epileptiform activity in tetanized hippocampal slices in vitro. Neuroscience101, 895–906 (2000).
  • Nilsen J , BrintonRD. Impact of progestins on estrogen-induced neuroprotection: synergy by progesterone and 19-norprogesterone and antagonism by medroxyprogesterone acetate.Endocrinology143, 205–212 (2002).
  • Watkins JC , JaneDE. The glutamate story.Br. J. Pharmacol.147(Suppl. 1), S100–S108 (2006).
  • Liu P , SmithPF, DarlingtonCL. Glutamate receptor subunits expression in memory-associated brain structures: regional variations and effects of aging.Synapse62(11), 834–841 (2008).
  • Fadalti M , PetragliaF, LuisiSet al. Changes of serum allopregnanolone levels in the first 2 years of life and during pubertal development. Pediatr. Res. 46(3), 323–327 (1999).
  • Kellogg CK , KenjarskiTP, PlegerGL, FryeCA. Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids.Brain Res.1067(1), 115–125 (2006).
  • Grobin AC , MorrowAL. 3α-hydroxy-5α-pregnan-20-one levels and GABA(A) receptor-mediated 36Cl(-) flux across development in rat cerebral cortex.Brain Res. Dev. Brain Res.131(1–2), 31–39 (2001).
  • Genazzani AR , PetragliaF, BernardiFet al. Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J. Clin. Endocrinol. Metab. 83, 2099–2103 (1998).
  • Purdy RH , MorrowAL, BlinnJR, PaulSM. Synthesis, metabolism, and pharmacological activity of 3a-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes.J. Med. Chem.33, 1572–1581 (1990).
  • Sundström I , BäckströmT. Citalopram increases pregnanolone sensitivity in patients with premenstrual syndrome: an open trial.Psychoneuroendocrinology23, 73–88 (1998a).
  • Sundström I , BäckströmT. Patients with premenstrual syndrome have decreased saccadic eye velocity compared to control subjects.Biol. Psych.44, 755–764 (1998b).
  • Wang M , SeippelL, PurdyRH, BäckströmT. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: study on serum pregnenolone, pregnenolone sulfate, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one.J. Clin. Endocrinol. Metab.81, 1076–1082 (1996).
  • Bixo M , AnderssonA, WinbladB, PurdyRH, BäckströmT. Progesterone, 5a-pregnane-3,20-dione and 3ahydroxy-5α-pregnane-20-one in specific regions of the human female brain in different endocrine states.Brain Res.764, 173–178 (1997).
  • Purdy RH , MorrowAL, MoorePH Jr, Paul SM. Stress-induced elevations of γ-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl Acad. Sci. USA88, 4553–4557 (1991).
  • Frye CA , VongherJM. 3α,5α-THP in the midbrain ventral tegmental area of rats and hamsters is increased in exogenous hormonal states associated with estrous cyclicity and sexual receptivity.J. Endocrinol. Invest.22(6), 455–464 (1999).
  • Frye CA , RhodesME, PetraliaSM, WalfAA, SumidaK, EdingerKL. 3α-Hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors.Neuroscience138(3), 1007–1014 (2006).
  • Frye CA , RhodesME. Infusions of 5α-pregnan-3α-ol-20-one (3α,5α-THP) to the ventral tegmental area, but not the substantia nigra, enhance exploratory, anti-anxiety, social and sexual behaviours and concomitantly increase 3α,5α-THP concentrations in the hippocampus, diencephalon and cortex of ovariectomised oestrogen-primed rats. J. Neuroendocrinol.18(12), 960–975 (2006).
  • Frye CA , ParisJJ, RhodesME. Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex.Reproduction133(3), 663–674 (2007).
  • Barrett AM . Probable Alzheimer’s disease: gender-related issues.J. Gend. Specif. Med.2(1), 55–60 (1999).
  • Brinton RD . A women’s health issue: Alzheimer’s disease and strategies for maintaining cognitive health.Int. J. Fertil. Womens Med.44(4), 174–185 (1999).
  • Fillit HM . The role of hormone replacement therapy in the prevention of Alzheimer’s Disease.Arch. Internal Med.162, 1934–1942 (2002).
  • Gao S , HendrieHC, HallKS, HuiS. The relationship between age, sex, and the incidence of dementia and Alzheimer’s Disease: a meta-analysis.Arch. Gen. Psych.55, 809–815 (1998).
  • Zandi PP , CarlsonMC, PlassmanBLet al. Hormone replacement therapy and the incidence of Alzheimers disease in older women: the Cache County Study. JAMA 28, 2123–2129 (2002).
  • Dunkin J , RasgonN, Wagner-StehK, DavidS, AltshulerL, RapkinA. Reproductive events modify the effects of estrogen replacement therapy on cognition in healthy postmenopausal women.Psychoneuroendocrinology30(3), 284–296 (2005).
  • Godfrey JR , El-BadriNS. Toward optimal health: advising aging women about dementia.J. Women’s Health (2009) (Epub ahead of print).
  • Smith CD , WeksteinDR, MarkesberyWR, FryeCA. 3α,5α-THP: a potential plasma neurosteroid biomarker in Alzheimer’s disease and perhaps non-Alzheimer’s dementia. Psychopharmacology86(3), 481–485 (2006).
  • Paganini-Hill A , HendersonVW. Estrogen deficiency and risk of Alzheimer’s disease in women.Am. J. Epidemiol.140, 256–261 (1994).
  • Resnick SM , HendersonVW. Hormone therapy and risk of Alzheimer disease: a critical time.JAMA288(17), 2170–2172 (2002).
  • Yaffe K . Hormone therapy and the brain: déjà vu all over again?JAMA289(20), 2717–2719 (2003).
  • Barrett-Connor E . Hormones and heart disease in women: the timing hypothesis.Am. J. Epidemiol.166(5), 506–510 (2007).
  • Pinna C , CignarellaA, SanvitoP, PelosiV, BolegoC. Prolonged ovarian hormone deprivation impairs the protective vascular actions of estrogen receptor α agonists.Hypertension51(4), 1210–1217 (2008).
  • Prentice RL , MansonJE, LangerRDet al. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am. J. Epidemiol. 170(1), 12–23 (2009).
  • Grady D , YaffeK, KristofM, LinF, RichardsC, Barrett-ConnorE. Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study.Am. J. Med.113(7), 543–548 (2002).
  • Rapp SR , EspelandMA, ShumakerSAet al. WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289(20), 2663–2672 (2003).
  • Shumaker SA , LegaultC, RappSRet al. WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289, 2651–2562 (2003).
  • Resnick SM , MakiPM, RappSRet al. Women’s Health Initiative Study of Cognitive Aging Investigators. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J. Clin. Endocrinol. Metab. 91(5), 1802–1810 (2006).
  • Sherwin BB . Affective changes with estrogen and androgen replacement therapy in surgically menopausal women.J. Affective Dis.14, 177–187 (1988).
  • Sherwin BB . Hormones, mood, and cognitive functioning in postmenopausal women.Obstet. Gynecol.87(Suppl. 2), S20–S26 (1996).
  • Sherwin BB . Estrogen effects on cognition in menopausal women.Neurology48(5, Suppl. 7), S21–S26 (1997).
  • Sherwin BB . Can estrogen keep you smart? Evidence from clinical studies.J. Psychiatr. Neurosci.24(4), 315–321 (1999).
  • Sherwin BB . Oestrogen and cognitive function throughout the female lifespan.Novartis Found Symp.230, 188–201 (2000).
  • Yoon BK , KimDK, KangYet al. Hormone replacement therapy in postmenopausal women with Alzheimer’s disease: a randomized, prospective study. Fertil. Steril. 79(2), 274–280 (2003).
  • Vongher JM , FryeCA. Progesterone in conjunction with estradiol has neuroprotective effects in an animal model of neurodegeneration.Pharmacol. Biochem. Behav.64(4), 777–785 (1999).
  • Rhodes ME , McCormickCM, FryeCA. 3α,5α-THP mediates progestins’ effects to protect against adrenalectomy-induced cell death in the dentate gyrus of female and male rats.Pharmacol. Biochem. Behav.78, 505–512 (2004).
  • Hoffman GE , MooreN, FiskumG, MurphyAZ. Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment.Exp. Neurol.182, 124–134 (2003).
  • Djebaili M , GuoQ, PettusEH, HoffmanSW, SteinDG. The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats.J. Neurotrauma22, 106–118 (2005).
  • Dohanich GP , FaderAJ, JavorskyDJ. Estrogen and estrogen–progesterone treatments counteract the effect of scopolamine on reinforced T-maze alternation in female rats.Behav. Neurosci.108, 988–992 (1994).
  • Koenig HL , SchumacherM, FerzazBet al. Progesterone synthesis and myelin formation by Schwann cells. Science 268(5216), 1500–1503 (1995).
  • Gibbs RB . Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats.Neurobiol. Aging21(1), 107–116 (2000).
  • Gibbs RB . Basal forebrain cholinergic neurons are necessary for estrogen to enhance acquisition of a delayed matching-to-position T-maze task.Horm. Behav.42(3), 245–257 (2002).
  • Harburger LL , BennettJC, FrickKM. Effects of estrogen and progesterone on spatial memory consolidation in aged females.Neurobiol. Aging28(4), 602–610 (2007).
  • Kask K , BäckströmT, NilssonLG, Sundström-PoromaaI. Allopregnanolone impairs episodic memory in healthy women.Psychopharmacology199(2), 161–168 (2008).
  • Maki PM , GastMJ, ViewegAJ, BurrissSW, YaffeK. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.Neurology69(13), 1322–1330 (2007).
  • Yates MA , MarkhamJA, AndersonSE, MorrisJR, JuraskaJM. Regional variability in age-related loss of neurons from the primary visual cortex and medial prefrontal cortex of male and female rats.Brain Res.1218, 1–12 (2008).
  • Pakkenberg B , PelvigD, MarnerLet al. Aging and the human neocortex. Exp. Gerontol. 38, 95–99 (2003).
  • Bodnoff SR , HumpreysAG, LehmannJCet al. Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity and hippocampal neuropathology in young and mid-aged rats. Behav. Brain Res. 62, 1–9 (1994).
  • Wallace M , FrankfurtM, ArellanosA, InagakiT, LuineV. Impaired recognition memory and decreased prefrontal cortex spine density in aged female rats.Ann. NY Acad. Sci.1097, 54–57 (2007).
  • Stein DG , WrightDW, KellermannAL. Does progesterone have neuroprotective properties?Ann. Emerg. Med.51(2), 164–172 (2008).
  • Schumacher M , GuennounR, SteinDG, De Nicola AF. Progesterone: therapeutic opportunities for neuroprotection and myelin repair. Pharmacol. Ther.116(1), 77–106 (2007).
  • Stein DG . Progesterone exerts neuroprotective effects after brain injury.Brain Res. Rev.57(2), 386–397 (2008).
  • Gibson CL , MurphySP. Progesterone enhances functional recovery after middle cerebral artery occlusion in male mice.J. Cereb. Blood Flow Metab.24, 805–813 (2004).
  • Cervantes M , Gonzalez-VidalMD, RuelasR, EscobarA, MoraliG. Neuroprotective effects of progesterone on damage elicited by acute global cerebral ischemia in neurons of the caudate nucleus,Arch. Med. Res.33, 6–14 (2002).
  • Chavez-Delgado ME , Mora-GalindoJ, Gomez-PinedoUet al. Facial nerve regeneration through progesterone-loaded chitosan prosthesis. A preliminary report. J. Biomed. Mater. Res. B Appl. Biomater. 67, 702–711 (2003).
  • Ishrat T , SayeedI, AtifF, SteinDG. Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats.Brain Res.1257, 94–101 (2009).
  • Fee DB , SwartzKR, JoyKM, RobertsKN, ScheffNN, ScheffSW. Effects of progesterone on experimental spinal cord injury.Brain Res.1137, 146–152 (2007).
  • Van Landingham JW , CekicM, CutlerSMet al. Progesterone and its metabolite allopregnanolone differentially regulate hemostatic proteins after traumatic brain injury. J. Cereb Blood Flow Metab. 28(11), 1786–1794 (2008).
  • Yankner BA , LuT, LoerchP. The aging brain.Annu. Rev. Pathol.3, 41–66 (2008).
  • Luine V , RodriguezM. Effects of estradiol on radial arm maze performance of young and aged rats.Behav. Neural. Biol.62(3), 230–236 (1994).
  • Bimonte-Nelson HA , SingletonRS, WilliamsBJ, GranholmAC. Ovarian hormones and cognition in the aged female rat: II. progesterone supplementation reverses the cognitive enhancing effects of ovariectomy.Behav. Neurosci.118(4), 707–714 (2004).
  • Warren SG , JuraskaJM. Sex differences and estropausal phase effects on water maze performance in aged rats.Neurobiol. Learn Mem.74(3), 229–240 (2000).
  • Frye CA , RhodesME, PetraliaSM, WalfAA, SumidaK, EdingerKL. 3α-Hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors.Neuroscience138, 1007–1014 (2006).
  • Leskiewicz M , BudziszewskaB, Jaworska-FeilL, KajtaM, LasonW. Effect of neurosteroids on glutamate binding sites and glutamate uptake in rat hippocampus.Pol. J. Pharmacol.50, 355–360 (1998).
  • Wang JM , IrwinRW, LiuL, ChenS, BrintonRD. Regeneration in a degenerating brain: potential of allopregnanolone as a neuroregenerative agent.Curr. Alzheimer Res.4, 510–517 (2007).
  • Wang C , MarxCE, MorrowAL, WilsonWA, MooreSD. Neurosteroid modulation of GABAergic neurotransmission in the central amygdala: a role for NMDA receptors.Neurosci. Lett.415, 118–123 (2007b).
  • Frye CA , DuffyCK, WalfAA. Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task.Neurobiol. Learn Mem.88(2), 208–216 (2007).
  • Sandstrom NJ , WilliamsCL. Memory retention is modulated by acute estradiol and progesterone replacement.Behav. Neurosci.115(2), 384–393 (2001).
  • Gibbs RB . Long-term treatment with estrogen and progesterone enhances acquisition of a spatial memory task by ovariectomized aged rats.Neurobiol. Aging21, 107–111 (2000).
  • Sato T , TanakaK, OhnishiY, TeramotoT, IrifuneM, NishikawaT. Effects of estradiol and progesterone on radial maze performance in middle-aged female rats fed a low-calcium diet.Behav. Brain Res.150(1–2), 33–42 (2004).
  • Eichenbaum H , SchoenbaumG, YoungB, BunseyM. Functional organization of the hippocampal memory system.Proc. Natl Acad. Sci. USA93(24), 13500–13507 (1996).
  • Fellows LK . Advances in understanding ventromedial prefrontal function: the accountant joins the executive.Neurology68(13), 991–995 (2007).
  • Osaka N , OsakaM. Striatal reward areas activated by implicit laughter induced by mimic words in humans: a functional magnetic resonance imaging study.Neuroreport16(15), 1621–1624 (2005).
  • Fanselow MS , PoulosAM. The neuroscience of mammalian associative learning.Annu. Rev. Psychol.56, 207–234 (2005).
  • Steinmetz JE , LavondDG, IvkovichD, LoganCG, ThompsonRF. Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system or a simple performance deficit?J. Neurosci.12(11), 4403–4426 (1992).
  • LeDoux JE . Emotional memory systems in the brain.Behav. Brain Res.58(1–2), 69–79 (1993).
  • Wagner AK , WillardLA, KlineAEet al. Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury. Brain Res. 998(1), 113–121 (2004).
  • Attella MJ , NattinvilleA, SteinDG. Hormonal state affects recovery from frontal cortex lesions in adult female rats.Behav. Neural Biol.48(3), 352–367 (1987).
  • O‘Connor CA , CernakI, JohnsonF, VinkR. Effects of progesterone on neurologic and morphologic outcome following diffuse traumatic brain injury in rats.Exp. Neurol.205(1), 145–153 (2007).
  • Carroll JC , RosarioER, PikeCJ. Progesterone blocks estrogen neuroprotection from kainate in middle-aged female rats.Neurosci. Lett.445(3), 229–232 (2008).
  • Ladurelle N , EychenneB, DentonDet al. Prolonged intracerebroventricular infusion of neurosteroids affects cognitive performances in the mouse. Brain Res. 858(2), 371–379 (2000).
  • van Wingen G , van BroekhovenF, VerkesRJet al. How progesterone impairs memory for biologically salient stimuli in healthy young women. J. Neurosci.27(42), 11416–11423 (2007).
  • Diaz-Veliz G , SotoV, DussaubatN, MoraS. Influence of the estrous cycle, ovariectomy and estradiol replacement upon the acquisition of conditioned avoidance responses in rats.Physiol. Behav.46(3), 397–401 (1989).
  • Wood GE , BeylinAV, ShorsTJ. The contribution of adrenal and reproductive hormones to the opposing effects of stress on trace conditioning in males versus females.Behav. Neurosci.115, 175–187 (2001).
  • Frye CA . Estrus-associated decrements in a water maze task are limited to acquisition.Physiol. Behav.57(1), 5–14 (1995).
  • Warren SG , JuraskaJM. Spatial and nonspatial learning across the rat estrous cycle.Behav. Neurosci.111(2), 259–266 (1997).
  • Rubinow MJ , ArseneauLM, BeverlyJL, JuraskaJM. Effect of the estrous cycle on water maze acquisition depends on the temperature of the water.Behav. Neurosci.118(4), 863–868. (2004)
  • Maki PM , RichJB, RosenbaumRS. Implicit memory varies across the menstrual cycle: estrogen effects in young women.Neuropsychologia40, 518–529 (2002).
  • Rosenberg L , ParkS. Verbal and spatial functions across the menstrual cycle in healthy young women.Psychoneuroendocrinology27, 835–841 (2002).
  • Barbaccia ML , RoscettiG, TrabucchiMet al. Time-dependent changes in rat brain neuroactive steroid concentrations and GABAA receptor function after acute stress. Neuroendocrinology 63, 166–172 (1996).
  • Drugan RC , HolmesPV, ScherDM, LuczakS, OhH, FerlandRJ. Environmentally induced changes in peripheral benzodiazepine receptors are stressor and tissue specific.Pharmacol. Biochem. Behav.50, 551–562 (1995).
  • Patchev VK , HassanAH, HolsboerDF, AlmeidaOF. The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus.Neuropsychopharmacology15, 533–540 (1996).
  • Patchev VK , ShoaibM, HolsboerF, AlmeidaOF. The neurosteroid tetrahydroprogesterone counteracts corticotropinreleasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus.Neuroscience62, 265–271 (1994).
  • Paris JJ , FryeCA. Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks.Reproduction136(1), 105–115 (2008).
  • Concas A , MostallinoMC, PorcuPet al. Role of brain allopregnanolone in the plasticity of γ-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery. Proc. Natl Acad. Sci. USA 95(22), 13284–13289 (1998).
  • Johansson I , BirznieceV, LindbladC, OlssonT, BäckströmT. Allopregnanolone inhibits learning in the Morris water maze.Brain Res.934(2), 125–131 (2002).
  • Bodensteiner KJ , CainP, RayAS, HamulaLA. Effects of pregnancy on spatial cognition in female Hooded Long-Evans rats.Horm. Behav.49(3), 303–314 (2006).
  • Gilbert Evans SE , RossLE, SellersEM, PurdyRH, RomachMK. 3α-Reduced neuroactive steroids and their precursors during pregnancy and the postpartum period.Gynecol. Endocrinol.21(5), 268–279 (2005).
  • Keenan PA , YaldooDT, StressME, FuerstDR, GinsburgKA. Explicit memory in pregnant women.Am. J. Obstet. Gynecol.179(3), 731–737 (1998).
  • Nierop A , BratsikasA, KlinkenbergA, NaterUM, ZimmermannR, EhlertU. Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary α-amylase responses to psychosocial stress in human pregnancy.J. Clin. Endocrinol. Metab.91(4), 1329–1335 (2006).
  • Weinstock M . Alterations induced by gestational stress in brain morphology and behaviour of the offspring.Prog. Neurobiol.65, 427–451 (2001).
  • Weinstock M . The potential influence of maternal stress hormones on development and mental health of the offspring.Brain Behav. Immun.19, 296–308 (2005).
  • Weinstock M . Gender differences in the effects of prenatal stress on brain development and behaviour.Neurochem. Res.32, 1730–1740 (2007).
  • Patchev VK , HassanAH, HolsboerDF, AlmeidaOF. The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus.Neuropsychopharmacology15(6), 533–540 (1996).
  • Sharp K , BrindlePM, BrownMW, TurnerGM. Memory loss during pregnancy.BJOG100, 209–215 (1993).
  • Frye CA , SturgisJD. Neurosteroids affect spatial/reference, working, and long-term memory of female rats,Neurobiol. Learn. Mem.64, 83–96 (1995).
  • Frye CA , WalfAA. Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks.Neurobiol. Learn Mem.90(1), 171–177 (2008).
  • Frye CA , RhodesME, DudekB. Estradiol to aged female or male mice improves learning in inhibitory avoidance and water maze tasks.Brain Res.1036(1–2), 101–108 (2005).
  • Warren SG , JuraskaJM. Sex differences and estropausal phase effects on water maze performance in aged rats.Neurobiol. Learn Mem.74(3), 229–240 (2000).
  • Frye CA . Estrus-associated decrements in a water maze task are limited to acquisition.Physiol. Behav.57(1), 5–14 (1995).
  • El-Bakri NK , IslamA, ZhuS, ElhassanA, MohammedA, WinbladB, AdemA. Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance.J. Cell Mol. Med.8(4), 537–544 (2004).
  • Johansson IM , BirznieceV, LindbladC, OlssonT, BäckströmT. Allopregnanolone inhibits learning in the Morris water maze.Brain Res.934(2), 125–131 (2002).
  • Frye CA , WalfAA. Progesterone enhances performance of aged mice in cortical or hippocampal tasks.Neurosci. Lett.437(2), 116–120 (2008).
  • Rhodes ME , FryeCA. Estrogen has mnemonic-enhancing effects in the inhibitory avoidance task.Pharmacol. Biochem. Behav.78(3), 551–558 (2004).
  • Korol DL , KoloLL. Estrogen-induced changes in place and response learning in young adult female rats.Behav. Neurosci.116(3), 411–420 (2002).
  • Zou LB , YamadaK, SasaM, NakataY, NabeshimaT. Effects of sigma(1) receptor agonist SA4503 and neuroactive steroids on performance in a radial arm maze task in rats.Neuropharmacology39(9), 1617–1627 (2000).
  • Korneyev A , CostaE. Allopregnanolone (THP) mediates anesthetic effects of progesterone in rat brain.Horm. Behavior30, 37–43 (1996).
  • Fahmy K , Abdel-RazikM, ShaarawayMet al. Effect of long-acting progestagen-only injectable contraceptives on carbohydrate metabolism and its hormonal profile. Contraception 44(4), 419–430 (1991).
  • Kahn HS , CurtisKM, MarchbanksPA. Effects of injectable or implantable progestin-only contraceptives on insulin–glucose metabolism and diabetes risk.Diabetes Care26(1), 216–225 (2003).
  • Spellacy WN , BuhiWC, BirkSA. The effect of the progestogen ethynodiol diacetate on glucose, insulin, and growth hormone after six months treatment.Acta Endocrinol.70(2), 373–384 (1972).
  • Vermeulen A , ThieryM. Hormonal contraceptives and carbohydrate tolerance. II. Influence of medroxyprogesterone acetate and chronic oral contraceptives.Diabetologia10(4), 253–259 (1974).
  • Amatayakul K , SivassomboonB, SingkamaniR. Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women.Contraception21(3), 283–297 (1980).
  • Amatayakul K , UttaravichaiC, SingkamaniR, RuckphaopuntS. Vitamin metabolism and the effects of multivitamin supplementation in oral contraceptive users.Contraception30(2), 179–196 (1984).
  • Dhall K , KumarM, RastogiGK, DeviPK. Short-term effects of norethisterone oenanthate and medroxyprogesterone acetate on glucose, insulin, growth hormone, and lipids.Fertil. Steril.28(2), 156–158 (1977).
  • Gold PE . Role of glucose in regulating the brain and cognition.Am. J. Clin. Nutr.61(Suppl. 4), S987–S995 (1995).
  • Berman KF , SchmidtPJ, RubinowDRet al. Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women. Proc. Natl Acad. Sci. USA 94, 8836–8841 (1997).
  • Hampson E . Variations in sex-related cognitive abilities across the menstrual cycle.Brain Cogn.14, 26–43 (1990).
  • Solis-Ortiz S , GuevaraMA, Corsi-CabreraM. Performance in a test demanding prefrontal functions is favored by early luteal phase progesterone: an electroencephalographic study.Psychoneuroendocrinology29, 1047–1057 (2004).
  • Phillips SM , SherwinBB. Variations in memory function and sex steroid hormones across the menstrual cycle.Psychoneuroendocrinology17, 497–506 (1992).
  • Poser CM , KassirerM, PeyserJM. Benign encephalopathy of pregnancy. Preliminary clinical observations.Acta Neurol. Scand.73, 39–43 (1986).
  • Gorzalka BB , WilkieDM, HansonLA. Discrimination of ovarian steroids by rats.Physiol. Behav.58(5), 1003–1011 (1995).
  • Grigorova M , SherwinBB. No differences in performance on test of working memory and executive functioning between healthy elderly postmenopausal women using or not using hormone therapy.Climacteric9(3), 181–194 (2006).
  • Ping SE , TrieuJ, WlodekME, BarrettGL. Effects of estrogen on basal forebrain cholinergic neurons and spatial learning.J. Neurosci. Res.86(7), 1588–1598 (2008).
  • Feng Z , ChengY, ZhangJT. Long-term effects of melatonin or 17 β-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats.J. Pineal Res.37(3), 198–206 (2004).
  • Beach FA . Daniel Berlyne Memorial Lecture. Hormones and psychological processes.Can. J. Psychol.37(2), 193–210 (1983).
  • Diaz-Veliz G , UrrestaF, DussaubatN, MoraS. Progesterone effects on the acquisition of conditioned avoidance responses an other motoric behaviors in intact and ovariectomized rats.Psychoneuroendocrinology19, 387–394 (1994).
  • Caggiula AR , DonnyEC, WhiteARet al. Environmental stimuli promote the acquisition of nicotine self-administration in rats. Psychopharmacology 163, 230–237 (2002).
  • González-Flores O , CamachoFJ, Domínguez-SalazarEet al. Progestins and place preference conditioning after paced mating. Horm. Behav. 46(2), 151–157 (2004).
  • Clark AS , KeltonMC, GuarraciFA, ClyonsEQ. Hormonal status and test condition, but not sexual experience, modulate partner preference in female rats.Horm. Behav.45(5), 314–323 (2004).
  • Frye CA , BayonLE, PursnaniNK, PurdyRH. The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats.Brain Res.808(1), 72–83 (1998).
  • Frye CA , RhodesME. The role of midbrain 3α,5α-THP in mediating exploration, anxiety, social and reproductive behaviour. In: Neuroactive Steroids in Brain: From Experiments to Psychopathology and Treatment. Ritsner MS, Weizman A (Eds.), Springer, The Netherlands (2008).
  • Frye CA , ParisJJ, RhodesME. Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex.Reproduction133, 663–174 (2007).
  • Frye CA , ParisJJ, RhodesME. Estrogen is necessary for 5α-pregnan-3α-ol-20-one (3α,5α-THP) infusion to the ventral tegmental area to facilitate social and sexual, but neither exploratory nor affective behavior of ovariectomized rats.Pharmacol. Biochem. Behav.91(2), 261–270 (2008).
  • Frye CA , WalfAA. Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways.Steroids73(9–10), 906–913 (2008).
  • Frye CA . Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse.Pharmacol. Biochem. Behav.86(2), 209–219 (2007).
  • Febo M , González-RodríguezLA, Capó-RamosDE, González-SegarraNY, SegarraAC. Estrogen-dependent alterations in D2/D3-induced G protein activation in cocaine-sensitized female rats.J. Neurochem.86(2), 405–412 (2003).
  • Eiler WJ , JuneHL. Blockade of GABAA receptors within the extended amygdala attenuates D(2) regulation of alcohol-motivated behaviors in the ventral tegmental area of alcohol-preferring (P) rats. Neuropharmacology52(8), 1570–1579 (2007).
  • Frye CA , BayonLE, PursnaniNK, PurdyRH. The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats.Brain Res.808(1), 72–83 (1998).
  • Chen HH , YangYK, YehTLet al. Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice. Chin. J. Physiol. 46(4), 169–174 (2003).
  • Russo SJ , FestaED, FabianSJet al. Gonadal hormones differentially modulate cocaine-induced conditioned place preference in male and female rats. Neuroscience 120(2), 523–533 (2003).
  • Heinsbroek RP , van Haaren F, Zantvoord F, van de Poll NE. Discriminative stimulus properties of pentobarbital and progesterone in male and female rats. Pharmacol. Biochem. Behav.28(3), 371–374 (1987).
  • Stewart J , KrebsWH, KaczenderE. State-dependent learning produced with steroids.Nature216, 1223–1224 (1967).
  • De Beun R , JansenE, SlangenJL, Van de Poll NE. Testosterone as appetitive and discriminative stimulus in rats: sex- and dose-dependent effects. Physiol. Behav.52(4), 629–634 (1992).
  • De Beun R . Hormones of the hypothalamo–pituitary–gonadal axis in drug discrimination learning.Pharmacol. Biochem. Behav.64(2), 311–317 (1999).
  • Heinsbroek RPW , Van Haaren F, Zantvoord F, Van de Poll NE. Discriminative stimulus properties of pentobarbital and progesterone in male and female rats. Pharmacol. Biochem. Behav.28, 371–374 (1987).
  • Chambers KC . Progesterone, estradiol, testosterone and dihydrotestosterone: effects on rate of extinction of a conditioned taste aversion in rats.Physiol. Behav.24(6), 1061–1065 (1980).
  • Janes C , CaseyP, HuntsdaleC, AngusG. Memory in pregnancy. I: subjective experiences and objective assessment of implicit, explicit and working memory in primigravid and primiparous women.J. Psychosom. Obstet. Gynaecol.20(2), 80–87 (1987).
  • Pause BM , SojkaB, KrauelK, Fehm-WolfsdorfG, FerstlR. Olfactory information processing during the course of the menstrual cycle.Biol. Psychol.44(1), 31–54 (1996).
  • Bajaj P , Arendt-NielsenL, BajajP, MadsenH. Sensory changes during the ovulatory phase of the menstrual cycle in healthy women.Eur. J. Pain.5(2), 135–144 (2001).
  • Barris MC , DawsonWW, TheissCL. The visual sensitivity of women during the menstrual cycle.Doc. Ophthalmol.49(2), 293–301 (1980).
  • Kis Z , BudaiD, ImreG, FarkasT, HorváthS, ToldiJ. The modulatory effect of estrogen on the neuronal activity in the barrel cortex of the rat. An electrophysiological study.Neuroreport12(11), 2509–2512 (2001).
  • Pfaff D , MontgomeryM, LewisC. Somatosensory determinants of lordosis in female rats: behavioral definition of the estrogen effect.J. Comp. Physiol. Psychol.91(1), 134–145 (1977).
  • Birke LI , AndrewRJ, BestSM. Distractibility changes during the oestrous cycle of the rat.Anim. Behav.27(2), 597–601 (1979).
  • Graham EA , GlasserM. Relationship of pregnanediol level to cognitive behavior and mood.Psychosom. Med.47(1), 26–34 (1985).
  • de Lignières B , VincensM. Differential effects of exogenous oestradiol and progesterone on mood in post-menopausal women: individual dose/effect relationship.Maturitas4(1), 67–72 (1982).
  • Nofrey BS , Ben-ShaharOM, BrakeWG. Estrogen abolishes latent inhibition in ovariectomized female rats.Brain Cogn.66(2), 156–160 (2008).
  • Frye CA . The role of neurosteroids and non-genomic effects of progestins and androgens in mediating sexual receptivity of rodents.Brain Res. Rev.37, 201–222 (2001).
  • Frye CA . The role of neurosteroids and nongenomic effects of progestins in the ventral tegmental area in mediating sexual receptivity of rodents.Horm. Behav.40, 226–233 (2001).
  • Frye CA , RhodesME, PetraliaSM, WalfAA, SumidaK, EdingerKL. 3α-Hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors.Neuroscience138, 1007–1014 (2006).
  • Morris R . Developments of a water-maze procedure for studying spatial learning in the rat.J. Neurosci. Methods.11(1), 47–60 (1984).
  • Harburger LL , BennettJC, FrickKM. Effects of estrogen and progesterone on spatial memory consolidation in aged females.Neurobiol. Aging28(4), 602–610 (2007).
  • Frye CA , WalfAA. Progesterone has cognitive enhancing effects in mice independent of actions at intracellular progestin receptors.Neurosci. Lett. (2009) (Submitted).
  • Frye CA , WalfAA. Progesterone enhances performance of aged mice in cortical or hippocampal tasks.Neurosci. Lett.437(2), 116–120 (2008).
  • Frye CA , WalfAA. Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks.Neurobiol. Learn Mem.90(1), 171–177 (2008).
  • Frye CA , WalfAA. Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks.Neurobiol. Learn. Mem.90(1), 171–177 (2008).
  • Duffy CK , WalfAA, KoonceCJ, FryeCA. Progestogens that enhance 3α-5α-THP levels have mnemonic effects when administered to ovariectomized mice. Presented at: Society for Neuroscience, 38th Annual Meeting. Washington, DC, USA, 15–19 November 2008.
  • Ciriza I , CarreroP, FryeCA, Garcia-SeguraLM. Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective.J. Neurobiol.66(9), 916–928 (2006).
  • Aggleton JP , HuntPR, RawlinsJN. The effects of hippocampal lesions upon spatial and non-spatial tests of working memory.Behav. Brain Res.19(2), 133–146 (1986).
  • Walf AA , RhodesME, FryeCA. Ovarian steroids enhance object recognition in naturally cycling and ovariectomized, hormone-primed rats.Neurobiol. Learn Mem.86(1), 35–46 (2006).
  • Lewis MC , OrrPT, FrickKM. Differential effects of acute progesterone administration on spatial and object memory in middle-aged and aged female C57BL/6 mice.Horm. Behav.54(3), 455–462 (2008).
  • González-Flores O , CamachoFJ, Domínguez-SalazarEet al. Progestins and place preference conditioning after paced mating. Horm. Behav. 46(2), 151–157 (2004).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.