دورية أكاديمية
أعرض في EDS

Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats.

التفاصيل البيبلوغرافية
العنوان: Androgen synthesis inhibition increases behavioural flexibility and mPFC tyrosine hydroxylase in gonadectomized male rats.
المؤلفون: Tomm RJ; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Seib DR; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Kachkovski GV; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Schweitzer HR; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Tobiansky DJ; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Floresco SB; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada., Soma KK; Department of Psychology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada.
المصدر: Journal of neuroendocrinology [J Neuroendocrinol] 2022 Jun; Vol. 34 (6), pp. e13128. Date of Electronic Publication: 2022 May 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley & Sons Country of Publication: United States NLM ID: 8913461 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2826 (Electronic) Linking ISSN: 09538194 NLM ISO Abbreviation: J Neuroendocrinol Subsets: MEDLINE
أسماء مطبوعة: Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-
مواضيع طبية MeSH: Androgens*/pharmacology , Tyrosine 3-Monooxygenase*, Animals ; Male ; Prefrontal Cortex/physiology ; Rats ; Reversal Learning ; Testosterone/physiology
مستخلص: Behavioural flexibility is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone administration decreases behavioural flexibility. It is well known that testosterone is produced in the gonads, but testosterone is also produced in the brain, including the mPFC and other nodes of the mesocorticolimbic system. It is unclear how testosterone produced in the brain versus the gonads influences behavioural flexibility. Here, in adult male rats, we assessed the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI but not GDX reduced the number of errors to criterion and perseverative errors in a strategy set-shifting task. In Experiment 2, with a separate cohort of rats, ABI but not GDX reduced perseverative errors in a reversal learning task. In Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results indicate that neurosteroids regulate executive functions and that ABI treatment for prostate cancer might affect cognition.
(© 2022 British Society for Neuroendocrinology.)
References: Andrew RJ, Rogers LJ. Testosterone, search behaviour and persistence. Nature. 1972;237:343-346.
Archer J. Testosterone and persistence in mice. Anim Behav. 1977;25:479-488.
Thompson WR, Wright JS. “Persistence” in rats: Effects of testosterone. Physiological Psychology. 1979;7(3):291-294.
Wallin KG, Wood RI. Anabolic-androgenic steroids impair set-shifting and reversal learning in male rats. Eur Neuropsychopharmacol. 2015;25:583-590.
Hauger LE, Westlye LT, Bjørnebekk A. Anabolic androgenic steroid dependence is associated with executive dysfunction. Drug Alcohol Depend. 2020;208:107874.
Kritzer MF, Brewer A, Montalmant F, Davenport M, Robinson JK. Effects of gonadectomy on performance in operant tasks measuring prefrontal cortical function in adult male rats. Horm Behav. 2007;51:183-194.
Diekhof EK, Kraft S. The association between endogenous testosterone level and behavioral flexibility in young men - evidence from stimulus-outcome reversal learning. Horm Behav. 2017;89:193-200.
Welker KM, Carré JM. Individual differences in testosterone predict persistence in men. Eur J Pers. 2015;29:83-89.
Wood RI, Serpa RO. Anabolic-androgenic steroid abuse and cognitive impairment: testosterone IMPAIRS biconditional task performance in male rats. Behav Brain res. 2020;379:112339.
Birrell JM, Brown VJ. Medial frontal cortex mediates perceptual Attentional set shifting in the rat. J Neurosci. 2000;20:4320-4324.
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.
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.
Ragozzino ME, Wilcox C, Raso M, Kesner RP. Involvement of rodent prefrontal cortex subregions in strategy switching. Behav Neurosci. 1999;113:32-41.
Ghods-Sharifi S, Haluk DM, Floresco SB. Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning. Neurobiol Learn Mem. 2008;89:567-573.
Low KL, Ma C, Soma KK. Tyramide signal amplification permits Immunohistochemical analyses of androgen receptors in the rat prefrontal cortex. J Histochem Cytochem. 2017;65:295-308.
Low KL, Tomm RJ, Ma C, Tobiansky DJ, Floresco SB, Soma KK. Effects of aging on testosterone and androgen receptors in the mesocorticolimbic system of male rats. Horm Behav. 2020;120:104689.
Diotel N, Charlier TD, Lefebvre d'Hellencourt C, et al. Steroid transport, local synthesis, and signaling within the brain: roles in neurogenesis, Neuroprotection, and sexual behaviors. Front Neurosci. 2018;12:84.
Ubuka T, Tsutsui K. Review: neuroestrogen regulation of socio-sexual behavior of males. Front Neurosci. 2014;8. doi:10.3389/fnins.2014.00323.
Hojo Y, Hattori T-a, Enami T, et al. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017 and P450 aromatase localized in neurons. Proc Natl Acad Sci USA. 2004;101:865-870.
Hojo Y, Higo S, Kawato S, et al. Hippocampal synthesis of sex steroids and corticosteroids: Essential for modulation of synaptic plasticity. Front Endocrin. 2011;2:43.
Hojo Y, Okamoto M, Kato A, et al. Neurosteroid synthesis in adult female rat hippocampus, including androgens and allopregnanolone. J Steroids Hormon Sci. 2014;5(1). doi:10.4172/2157-7536.S4-002.
Kenealy BP, Kapoor A, Guerriero KA, et al. Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin releasing hormone release. J Neurosci. 2013;33:19051-19059.
Micevych P, Sinchak K. Synthesis and function of hypothalamic Neuroprogesterone in reproduction. Endocrinology. 2008;149:2739-2742.
Delville Y, Mansour KM, Ferris CF. Testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus. Physiol Behav. 1996;60:25-29.
Barker JM, Galea LAM. Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats. Neuroscience. 2008;152:888-902.
McClure RES, Barha CK, Galea LAM. 17β-estradiol, but not estrone, increases the survival and activation of new neurons in the hippocampus in response to spatial memory in adult female rats. Horm Behav. 2013;63:144-157.
Spritzer MD, Galea LAM. Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats. Devel Neurobio. 2007;67:1321-1333.
Vajaria R, Vasudevan N, Delivopoulos E, et al. The neuroprotective effects of estrogen in the prefrontal cortex in adult male mice. Virtual International Meeting STEROIDS AND NERVOUS SYSTEM; 2021. https://sites.google.com/view/neurosteroids2021/program.
Tobiansky DJ, Korol AM, Ma C, et al. Testosterone and Corticosterone in the Mesocorticolimbic system of male rats: effects of Gonadectomy and caloric restriction. Endocrinology. 2018;159:450-464.
Hernandez L, Gonzalez L, Murzi E, Páez X, Gottberg E, Baptista T. Testosterone modulates mesolimbic dopaminergic activity in male rats. Neurosci Lett. 1994;171:172-174.
Adler A, Vescovo P, Robinson JK, Kritzer MF. Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats. Neuroscience. 1999;89:939-954.
Kritzer MF. Effects of acute and chronic gonadectomy on the catecholamine innervation of the cerebral cortex in adult male rats: insensitivity of axons immunoreactive for dopamine-β-hydroxylase to gonadal steroids, and differential sensitivity of axons immunoreactive for tyrosine hydroxylase to ovarian and testicular hormones. J Comp Neurol. 2000;427:617-633.
Kritzer MF. Long-term gonadectomy affects the density of tyrosine hydroxylase- but not dopamine-beta-hydroxylase-, choline acetyltransferase- or serotonin-immunoreactive axons in the medial prefrontal cortices of adult male rats. Cereb Cortex. 2003;13(3):282-296.
Nicola C, Dubois M, Campart C, et al. The prostate cancer therapy Enzalutamide compared with Abiraterone acetate/prednisone impacts motivation for exploration, spatial learning and alters dopaminergic transmission in aged castrated mice. Cancer. 2021;13:3518.
Aubele T, Kritzer MF. Gonadectomy and hormone replacement affects in vivo basal extracellular dopamine levels in the prefrontal cortex but not motor cortex of adult male rats. Cereb Cortex. 2011;21:222-232.
Koss WA, Lloyd MM, Sadowski RN, Wise LM, Juraska JM. Gonadectomy before puberty increases the number of neurons and glia in the medial prefrontal cortex of female, but not male, rats: Prepubertal Gonadectomy and the mPFC. Dev Psychobiol. 2015;57:305-312.
Le Saux M, Morissette M, Di Paolo T. ERβ mediates the estradiol increase of D2 receptors in rat striatum and nucleus accumbens. Neuropharmacology. 2006;50:451-457.
Mermelstein P, Becker J, Surmeier D. Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor. J Neurosci. 1996;16:595-604.
Yoest KE, Quigley JA, Becker JB. Rapid effects of ovarian hormones in dorsal striatum and nucleus accumbens. Horm Behav. 2018;104:119-129.
Thompson TL, Moss RL. Estrogen regulation of dopamine release in the nucleus Accumbens: genomic-and nongenomic-mediated effects. J Neurochem. 2008;62:1750-1756.
Cunningham RL, Claiborne BJ, McGinnis MY. Pubertal exposure to anabolic androgenic steroids increases spine densities on neurons in the limbic system of male rats. Neuroscience. 2007;150:609-615.
Wallin-Miller K, Li G, Kelishani D, Wood RI. Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats. Neuroscience. 2016;330:72-78.
Purves-Tyson TD, Owens SJ, Double KL, Desai R, Handelsman DJ, Weickert CS. Testosterone induces molecular changes in dopamine signaling pathway molecules in the adolescent male rat Nigrostriatal pathway. PLoS ONE. 2014;9:e91151.
Yin L, Hu Q. CYP17 inhibitors-abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nat Rev Urol. 2014;11:32-42.
Committee for Medicinal Products for Human Use (CHMP). Assesment Report for Zytiga (Abiraterone). European Medicines Agency, 21 July 2011.
Locke JA, Guns ES, Lubik AA, et al. Androgen levels increase by Intratumoral De novo Steroidogenesis during progression of castration-resistant prostate cancer. Cancer res. 2008;68:6407-6415.
Barrie SE, Potter GA, Goddard PM, Haynes BP, Dowsett M, Jarman M. Pharmacology of novel steroidal inhibitors of cytochrome P45017 (17α-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol. 1994;50(5-6):267-273.
Frau R, Bini V, Pes R, et al. Inhibition of 17α-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation. Psychoneuroendocrinology. 2014;39:204-213.
Duc I, Bonnet P, Duranti V, et al. In vitro and in vivo models for the evaluation of potent inhibitors of male rat 17α-hydroxylase/C17,20-lyase. J Steroid Biochem Mol Biol. 2003;84(5):537-542.
Haidar S, Ehmer PB, Barassin S, Batzl-Hartmann C, Hartmann RW. Effects of novel 17α-hydroxylase/C17, 20-lyase (P450 17, CYP 17) inhibitors on androgen biosynthesis in vitro and in vivo. J Steroid Biochem Mol Biol. 2003;84(5):555-562.
Enomoto T, Tse MT, Floresco SB. Reducing prefrontal gamma-Aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia. Biol Psychiatry. 2011;69:432-441.
Butts KA, Floresco SB, Phillips AG. Acute stress impairs set-shifting but not reversal learning. Behav Brain res. 2013;252:222-229.
Tomm RJ, Tse MT, Tobiansky DJ, Schweitzer HR, Soma KK, Floresco SB. Effects of aging on executive functioning and mesocorticolimbic dopamine markers in male Fischer 344 × brown Norway rats. Neurobiol Aging. 2018;72:134-146.
Haluk DM, Floresco SB. Ventral striatal dopamine modulation of different forms of behavioral flexibility. Neuropsychopharmacology. 2009;34:2041-2052.
Taves MD, Ma C, Heimovics SA, Saldanha CJ, Soma KK. Measurement of steroid concentrations in brain tissue: methodological considerations. Front Endocrin. 2011;2:39. doi:10.3389/fendo.2011.00039.
Palkovits M. Isolated removal of hypothalamic or other brain nuclei of the rat. Brain res. 1973;59:449-450.
Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 6th ed. Elsevier, Academic Press; 2007.
Hamden JE, Salehzadeh M, Jalabert C, et al. Measurement of 11-dehydrocorticosterone in mice, rats and songbirds: effects of age, sex and stress. Gen Comp Endocrinol. 2019;281:173-182.
Heimovics SA, Prior NH, Maddison CJ, Soma KK. Rapid and widespread effects of 17β-estradiol on intracellular signaling in the male songbird brain: a seasonal comparison. Endocrinology. 2012;153(3):1364-1376.
Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676-682.
Tobiansky DJ, Kachkovski GV, Enos RT, Schmidt KL, Murphy EA, Soma KK. Sucrose consumption alters steroid and dopamine signalling in the female rat brain. J Endocrinol. 2020;245:231-246.
Matkowskyj KA, Schonfeld D, Benya RV. Quantitative immunohistochemistry by measuring cumulative signal strength using commercially available software Photoshop and Matlab. J Histochem Cytochem. 2000;48:303-311.
Castañé A, Theobald DEH, Robbins TW. Selective lesions of the dorsomedial striatum impair serial spatial reversal learning in rats. Behav Brain res. 2010;210:74-83.
George SA, Rodriguez-Santiago M, Riley J, Abelson JL, Floresco SB, Liberzon I. Alterations in cognitive flexibility in a rat model of post-traumatic stress disorder. Behav Brain res. 2015;286:256-264.
R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, https://www.R-project.org/; 2020.
Dalton GL, Ma LM, Phillips AG, Floresco SB. Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning. Psychopharmacology (Berl). 2011;216:525-535.
Ang JE, Olmos D, de Bono JS. CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer. Br J Cancer. 2009;100:671-675.
Spritzer MD, Gill M, Weinberg A, Galea LAM. Castration differentially affects spatial working and reference memory in male rats. Arch Sex Behav. 2008;37:19-29.
Spritzer MD, Daviau ED, Coneeny MK, Engelman SM, Prince WT, Rodriguez-Wisdom KN. Effects of testosterone on spatial learning and memory in adult male rats. Horm Behav. 2011;59:484-496.
Levay EA, Tammer AH, Penman J, Kent S, Paolini AG. Calorie restriction at increasing levels leads to augmented concentrations of corticosterone and decreasing concentrations of testosterone in rats. Nutr Res. 2010;30:366-373.
Govic A, Levay EA, Hazi A, Penman J, Kent S, Paolini AG. Alterations in male sexual behaviour, attractiveness and testosterone levels induced by an adult-onset calorie restriction regimen. Behav Brain res. 2008;190:140-146.
Handa RJ, Burgess LH, Kerr JE, O'Keefe JA. Gonadal steroid hormone receptors and sex differences in the Hypothalamo-pituitary-adrenal Axis. Horm Behav. 1994;28:464-476.
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.
Beas BS, McQuail JA, Bañuelos C, Setlow B, Bizon JL. Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats. Neuroscience. 2017;345:274-286.
Locklear MN, Michaelos M, Collins WF, Kritzer MF. Gonadectomy but not biological sex affects burst-firing in dopamine neurons of the ventral tegmental area and in prefrontal cortical neurons projecting to the ventral tegmentum in adult rats. Eur J Neurosci. 2017;45:106-120.
Aubele T, Kritzer MF. Androgen influence on prefrontal dopamine Systems in Adult Male Rats: localization of cognate intracellular receptors in medial prefrontal projections to the ventral tegmental area and effects of Gonadectomy and hormone replacement on glutamate-stimulated extracellular dopamine level. Cereb Cortex. 2012;22:1799-1812.
Wood RI, Armstrong A, Fridkin V, Shah V, Najafi A, Jakowec M. Roid rage in rats? Testosterone effects on aggressive motivation, impulsivity and tyrosine hydroxylase. Physiol Behav. 2013;110-111:6-12.
Beer TM, Bland LB, Bussiere JR, et al. Testosterone loss and estradiol administration modify memory in men. J Urol. 2006;175:130-135.
Thiery-Vuillemin A, Hvid Poulsen M, Lagneau E, et al. Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study. ESMO Open. 2018;3:e000397.
معلومات مُعتمدة: 169203 Canada CIHR
فهرسة مساهمة: Keywords: CYP17A1; dopamine; neurosteroids; set-shifting; testosterone
المشرفين على المادة: 0 (Androgens)
3XMK78S47O (Testosterone)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
تواريخ الأحداث: Date Created: 20220518 Date Completed: 20220707 Latest Revision: 20220729
رمز التحديث: 20231215
DOI: 10.1111/jne.13128
PMID: 35583989
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2826
DOI:10.1111/jne.13128