Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3).

Publisher: Informa Healthcare Country of Publication: England NLM ID: 9617529 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1607-8888 (Electronic) Linking ISSN: 10253890 NLM ISO Abbreviation: Stress Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: [Amsterdam?] : Harwood Academic Publishers

Serotonin*/metabolism ; Corticosterone*/pharmacology ; Progesterone*/pharmacology ; Estradiol*/pharmacology ; Behavior, Animal*/drug effects ; Hypothalamus*/metabolism ; Hypothalamus*/drug effects ; Organic Cation Transport Proteins*/metabolism ; Estrogens*; Animals ; Female ; Rats ; Ovariectomy ; Rats, Sprague-Dawley ; Microdialysis

Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E2), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E2-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E2. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E2 + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.

Neuropharmacology. 2006 Jun;50(8):941-52. (PMID: 16581093)
Brain Res. 2010 Apr 22;1326:105-13. (PMID: 20171957)
Physiol Behav. 2011 Aug 3;104(2):306-11. (PMID: 21081135)
Neuroendocrinology. 1983;36(3):235-41. (PMID: 6835476)
Neuroendocrinology. 1989 Jun;49(6):561-9. (PMID: 2475814)
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13941-6. (PMID: 9811905)
J Neurobiol. 1998 Sep 5;36(3):357-78. (PMID: 9733072)
Br J Pharmacol Chemother. 1965 Aug;25(1):34-49. (PMID: 19108208)
J Endocrinol. 1995 Feb;144(2):311-21. (PMID: 7706984)
J Neurosci. 1996 Nov 15;16(22):7151-60. (PMID: 8929424)
Neuroscience. 2011 May 19;182:105-14. (PMID: 21420472)
J Neurochem. 2008 Aug;106(3):1471-82. (PMID: 18513366)
J Neurosci. 1995 Mar;15(3 Pt 2):2272-9. (PMID: 7891165)
Pharmacol Biochem Behav. 2002 Mar;71(3):469-80. (PMID: 11830181)
Pharmacol Rev. 1999 Dec;51(4):593-628. (PMID: 10581325)
Neuroendocrinology. 1993 May;57(5):946-54. (PMID: 8413831)
J Biol Chem. 1998 Nov 20;273(47):30915-20. (PMID: 9812985)
Horm Behav. 2018 Aug;104:173-182. (PMID: 29738736)
J Neuroendocrinol. 2004 Dec;16(12):989-98. (PMID: 15667454)
Neuroendocrinology. 2004;80(3):152-7. (PMID: 15583472)
J Biol Chem. 1998 Dec 4;273(49):32776-86. (PMID: 9830022)
Neuroscience. 1985 Jul;15(3):891-902. (PMID: 2866468)
Proc Natl Acad Sci U S A. 2019 Apr 9;116(15):7503-7512. (PMID: 30898882)
J Cardiovasc Pharmacol. 2003 Dec;42 Suppl 1:S117-9. (PMID: 14871041)
Brain Res. 2001 Dec 27;923(1-2):103-11. (PMID: 11743977)
J Neuroendocrinol. 2005 Mar;17(3):179-85. (PMID: 15796770)
Horm Behav. 2009 Jun;56(1):149-57. (PMID: 19371745)
Rev Physiol Biochem Pharmacol. 1980;87:33-115. (PMID: 6999585)
J Comp Neurol. 2009 Feb 1;512(4):529-55. (PMID: 19025979)
Handb Exp Pharmacol. 2021;266:241-251. (PMID: 34104992)
Neuroscience. 2005;132(2):249-59. (PMID: 15802180)
Neuropsychopharmacology. 2001 Dec;25(6):881-91. (PMID: 11750181)
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 4;53:90-8. (PMID: 24657329)
Science. 1984 Dec 21;226(4681):1436-9. (PMID: 6209800)
Brain Res Bull. 1993;32(3):293-300. (PMID: 7690679)
Neuroendocrinology. 1983 Sep;37(3):218-24. (PMID: 6621803)
Endocrinology. 1974 Jun;94(6):1704-8. (PMID: 4857496)
J Neurosci. 2006 Aug 23;26(34):8758-66. (PMID: 16928864)
J Neurosci Methods. 1991 Jan;36(1):85-90. (PMID: 1676433)
Front Neuroendocrinol. 2002 Jan;23(1):41-100. (PMID: 11906203)
Naunyn Schmiedebergs Arch Pharmacol. 1999 Apr;359(4):303-9. (PMID: 10344529)
Biol Mood Anxiety Disord. 2012 Feb 07;2:3. (PMID: 22738383)
Pharmacol Biochem Behav. 2003 Aug;76(1):63-73. (PMID: 13679218)
Horm Behav. 1997 Jun;31(3):244-55. (PMID: 9213138)
Brain Res. 1996 Mar 4;711(1-2):84-92. (PMID: 8680878)
Brain Res Bull. 1987 Aug;19(2):195-202. (PMID: 3664280)
J Vis Exp. 2012 Sep 15;(67):e4389. (PMID: 23007862)
Neuropsychopharmacology. 2005 Jul;30(7):1288-301. (PMID: 15756306)
Pharmacol Ther. 2009 Jan;121(1):89-99. (PMID: 19022290)
Endocrinology. 1988 Aug;123(2):1110-8. (PMID: 2899499)
J Biol Chem. 1997 Apr 18;272(16):10408-13. (PMID: 9099681)
Brain Res. 1999 Jun 12;831(1-2):146-54. (PMID: 10411994)
Biol Psychiatry. 2006 Aug 1;60(3):288-95. (PMID: 16458260)
Front Neuroendocrinol. 2009 Jul;30(2):212-38. (PMID: 19394356)
Brain Res. 1993 Nov 5;627(1):9-16. (PMID: 8293308)
Neuropsychopharmacology. 2003 May;28(5):830-8. (PMID: 12637949)
J Comp Neurol. 1997 Dec 1;388(4):507-25. (PMID: 9388012)
Brain Res. 1983 Apr 4;264(2):344-8. (PMID: 6850308)
Endocrinology. 1986 Mar;118(3):1180-6. (PMID: 3948769)
Brain Res. 2006 Apr 21;1084(1):67-79. (PMID: 16545785)
Neuropsychopharmacology. 1999 Aug;21(2):312-20. (PMID: 10432479)
Psychopharmacology (Berl). 2002 Mar;160(3):271-82. (PMID: 11889496)
Eur J Pharmacol. 2007 Jan 19;555(1):67-75. (PMID: 17112509)
J Neuroendocrinol. 2004 Jun;16(6):516-24. (PMID: 15189326)
Mol Psychiatry. 2004 Jun;9(6):550-6. (PMID: 15164085)
Physiol Behav. 1970 Feb;5(2):137-41. (PMID: 5535791)
Horm Behav. 2003 Jan;43(1):254-62. (PMID: 12614657)
Neurosci Biobehav Rev. 2004 Mar;28(1):55-63. (PMID: 15036933)
Endocrinology. 1991 Nov;129(5):2503-11. (PMID: 1657578)
Front Behav Neurosci. 2013 Oct 01;7:136. (PMID: 24101897)
Endocrinology. 1987 Jul;121(1):298-304. (PMID: 3595521)
Brain Res. 2005 Nov 23;1063(1):69-76. (PMID: 16266691)
Rev Physiol Biochem Pharmacol. 2003;150:36-90. (PMID: 12827517)
Neuropharmacology. 1987 May;26(5):407-17. (PMID: 3037412)
Endocrinology. 1975 Jan;96(1):219-26. (PMID: 1167352)
J Neurosci. 2013 Jul 17;33(29):11800-10. (PMID: 23864669)
Brain Res Brain Res Rev. 2000 Sep;33(2-3):242-57. (PMID: 11011068)
Trends Neurosci. 1997 Feb;20(2):78-84. (PMID: 9023876)
Endocrinology. 2005 Apr;146(4):1650-73. (PMID: 15618360)
Stress. 2017 Mar;20(2):223-230. (PMID: 28345385)
Neuroendocrinology. 1987 Mar;45(3):201-7. (PMID: 3561695)
J Neurosci. 2004 Dec 1;24(48):10868-77. (PMID: 15574737)

P20 RR015567 United States RR NCRR NIH HHS; R01 DA019921 United States DA NIDA NIH HHS; R03 MH068303 United States MH NIMH NIH HHS; R03 MH068364 United States MH NIMH NIH HHS

Keywords: Extraneuronal monoamine transporter; OCT3; hypothalamus; lordosis; steroids; uptake2

333DO1RDJY (Serotonin)
W980KJ009P (Corticosterone)
4G7DS2Q64Y (Progesterone)
4TI98Z838E (Estradiol)
0 (Estrogens)
0 (Organic Cation Transport Proteins)

Date Created: 20250203 Date Completed: 20250505 Latest Revision: 20260605

20260606

PMC11801257

10.1080/10253890.2025.2457765

39898528