title: Opioid receptor-dependent sex differences in synaptic plasticity in the hippocampal mossy fiber pathway of the adult rat.
abstract: The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus.
authors: The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center, Departments of Child and Adolescent Psychiatry, and.
authors: Lauren C
authors: LC
authors: Harte-Hargrove
authors: The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center.
authors: Ada
authors: A
authors: Varga-Wesson
authors: The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center, Departments of Child and Adolescent Psychiatry, and.
authors: Aine M
authors: AM
authors: Duffy
authors: Weill Cornell Medical College, Brain and Mind Research Institute, New York, New York 10065, and The Rockefeller University, Laboratory of Neuroendocrinology, New York, New York 10065.
authors: Teresa A
authors: http://orcid.org/0000-0002-0458-6569
authors: TA
authors: Milner
authors: The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center, Departments of Child and Adolescent Psychiatry, and Physiology and Neurosci, Psychiatry, New York, New York 10016, hscharfman@nki.rfmh.org.
authors: Helen E
authors: http://orcid.org/0000-0003-4006-3383
authors: HE
authors: Scharfman
mesh_terms: D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism*; D012727:Sex Characteristics; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*
chemical_list: D058787:GABA-A Receptor Antagonists; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; C017069:bicuculline methiodide; D013004:Somatostatin; D001418:Baclofen; C080629:saclofen; D001640:Bicuculline
keywords: area CA3; estrous cycle; hippocampus; long-term potentiation; opiate; sex differences
references: Brain Res. 1993 Jan 22;601(1-2):129-35
references: 8381696
references: Mol Pharmacol. 1992 May;41(5):822-31
references: 1317000
references: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13304-9
references: 8917586
references: Brain Res. 1994 Oct 24;661(1-2):25-34
references: 7834376
references: J Neurosci. 1995 Oct;15(10):6939-45
references: 7472450
references: Front Neural Circuits. 2012 May 16;6:23
references: 22623913
references: Int Rev Cytol. 1990;121:67-126
references: 1972143
references: J Neurosci. 2013 Feb 6;33(6):2338-55
references: 23392664
references: Psychopharmacology (Berl). 1989;98(3):408-11
references: 2501818
references: Brain Res Bull. 1991 Aug;27(2):219-23
references: 1660336
references: Prog Brain Res. 2007;163:245-63
references: 17765723
references: Neurosci Res. 2005 May;52(1):1-9
references: 15811547
references: J Neurosci. 1992 Jul;12(7):2745-50
references: 1319480
references: J Neurosci. 1992 Aug;12(8):3217-25
references: 1353794
references: Annu Rev Physiol. 2002;64:355-405
references: 11826273
references: Prog Brain Res. 2007;163:3-22
references: 17765709
references: Neuroscience. 2001;104(3):741-59
references: 11440806
references: Synapse. 2013 Nov;67(11):757-72
references: 23720407
references: Cell. 1994 Oct 7;79(1):69-79
references: 7923379
references: Genes Brain Behav. 2003 Apr;2(2):80-92
references: 12884965
references: J Neurochem. 2001 Mar;76(6):1887-94
references: 11259507
references: Brain Res. 2006 Dec 18;1126(1):183-7
references: 16945354
references: J Chem Neuroanat. 2014 Jan;55:9-17
references: 24275289
references: J Neurosci. 2009 Oct 14;29(41):12982-93
references: 19828812
references: J Neurosci. 2001 Sep 1;21(17):6532-43
references: 11517242
references: Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3366-70
references: 21245308
references: Brain Res. 2009 Feb 27;1257:65-74
references: 19133236
references: Neuropharmacology. 2010 Jan;58(1):233-40
references: 19596017
references: J Comp Neurol. 1997 May 12;381(3):373-87
references: 9133574
references: Epilepsy Res Suppl. 1992;7:187-95
references: 1361330
references: J Neurophysiol. 2007 Mar;97(3):2301-11
references: 17215502
references: Neuropharmacology. 2014 Jan;76 Pt C:696-708
references: 23660230
references: J Comp Neurol. 1981 Jan 1;195(1):51-86
references: 7204652
references: Eur J Neurosci. 2010 Aug;32(4):625-31
references: 20626460
references: Front Endocrinol (Lausanne). 2011 Aug 19;2(18):null
references: 22468144
references: Mol Pharmacol. 1993 May;43(5):684-93
references: 8388986
references: J Pharmacol Exp Ther. 1992 Nov;263(2):725-33
references: 1359112
references: Neurosci Lett. 1993 Oct 14;161(1):53-6
references: 8255546
references: Exp Clin Psychopharmacol. 2006 Feb;14(1):34-41
references: 16503703
references: Front Neuroendocrinol. 2015 Jan;36:72-89
references: 25159586
references: Nat Methods. 2014 Jun;11(6):629-32
references: 24776635
references: J Neurosci Res. 2000 Aug 15;61(4):371-5
references: 10931523
references: Brain Res. 1999 Mar 13;821(2):286-93
references: 10064815
references: Trends Pharmacol Sci. 2011 Sep;32(9):521-33
references: 21680031
references: Epilepsia. 1998 Dec;39(12):1243-52
references: 9860058
references: J Neurosci. 1995 May;15(5 Pt 2):3788-95
references: 7751946
references: J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):343-8
references: 7626478
references: Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S130-42
references: 19596521
references: Trends Neurosci. 1988 Jul;11(7):308-14
references: 2465635
references: Brain Res. 1991 Oct 18;562(1):57-65
references: 1666016
references: J Pharmacol Exp Ther. 2013 Nov;347(2):258-64
references: 23978562
references: Neurobiol Learn Mem. 2011 Feb;95(2):206-20
references: 21224009
references: Biochim Biophys Acta. 2010 Oct;1800(10):1030-44
references: 19909788
references: Brain Res. 2008 Sep 26;1232:70-84
references: 18691558
references: Neurosci Lett. 2001 Aug 31;309(3):207-9
references: 11514077
references: Brain Res. 2013 Jun 13;1514:123-7
references: 23415935
references: Neuroscientist. 2014 Oct;20(5):534-45
references: 24510074
references: Brain Res. 2011 Jan 25;1370:215-9
references: 21075087
references: Epilepsia. 2010 Jul;51 Suppl 3:141-4
references: 20618420
references: Neuropeptides. 1983 Dec;4(1):45-50
references: 6669222
references: Int J Neurosci. 1992 Jul-Aug;65(1-4):117-29
references: 1341673
references: J Neurophysiol. 1999 Feb;81(2):925-9
references: 10036289
references: J Neurosci. 2003 Dec 17;23(37):11641-52
references: 14684866
references: Behav Brain Res. 2011 Oct 10;224(1):112-20
references: 21664381
references: Brain Res. 1995 Dec 12;703(1-2):26-30
references: 8719612
references: Pharmacol Biochem Behav. 2003 Feb;74(3):541-9
references: 12543217
references: Brain Res Bull. 2001 Jan 15;54(2):131-40
references: 11275401
references: Hippocampus. 1999;9(3):255-76
references: 10401641
references: Prog Brain Res. 2007;163:109-32
references: 17765714
references: Neuroscience. 1996 Apr;71(3):671-90
references: 8867040
references: Brain Res. 1999 Dec 4;849(1-2):203-15
references: 10592303
references: Science. 1980 Aug 29;209(4460):1017-8
references: 7190730
references: J Comp Neurol. 2000 Apr 3;419(2):244-56
references: 10723002
references: Gend Med. 2010 Oct;7(5):402-13
references: 21056867
references: Eur J Neurosci. 1999 Dec;11(12):4476-80
references: 10594677
references: Front Integr Neurosci. 2012 May 23;6:23
references: 22654741
references: J Neurophysiol. 1997 Aug;78(2):1082-95
references: 9307136
references: Pharmacol Biochem Behav. 2004 Jun;78(2):199-207
references: 15219759
references: J Neurosci. 1994 Jul;14(7):4244-51
references: 8027776
references: Brain Res. 1992 Apr 24;578(1-2):33-40
references: 1324765
references: J Neurophysiol. 1993 Feb;69(2):630-5
references: 8096243
references: J Psychiatry Neurosci. 2000 Jan;25(1):33-42
references: 10721682
references: Neurobiol Learn Mem. 2001 Nov;76(3):239-52
references: 11726235
references: Hippocampus. 2012 Mar;22(3):516-33
references: 21254303
references: BMC Neurosci. 2001;2:20
references: 11801187
references: Neurosci Biobehav Rev. 2004 Oct;28(6):533-46
references: 15527861
references: Neuroscience. 2013 Jun 3;239:46-66
references: 23276673
references: Neuroscience. 2006;138(3):837-44
references: 16310960
references: Brain Res. 1998 Nov 16;811(1-2):40-6
references: 9804884
references: J Neurosci. 2006 Aug 16;26(33):8517-22
references: 16914677
references: J Comp Neurol. 2004 Jan 26;469(1):107-18
references: 14689476
references: Cell Tissue Res. 2011 Sep;345(3):285-94
references: 21826442
references: Neuroscience. 2009 Mar 3;159(1):204-16
references: 19150393
references: Neuroscience. 1999;94(2):465-71
references: 10579209
references: Methods Mol Biol. 2011;793:23-59
references: 21913092
references: J Neurosci. 2009 Feb 4;29(5):1457-68
references: 19193892
references: Eur J Neurosci. 2007 Nov;26(9):2595-612
references: 17970745
references: Biol Sex Differ. 2012 Jun 07;3(1):14
references: 22676718
references: Exp Brain Res. 1991;87(3):537-45
references: 1783024
references: Int Rev Neurobiol. 1996;39:145-96
references: 8894847
references: J Neurosci. 2011 Nov 23;31(47):16897-906
references: 22114260
references: Brain Res. 2013 Jun 26;1518:71-81
references: 23583481
references: Hippocampus. 1996;6(4):347-470
references: 8915675
references: Horm Behav. 1998 Oct;34(2):140-8
references: 9799624
references: Neurotoxicol Teratol. 2002 Jan-Feb;24(1):5-16
references: 11836067
references: J Neurosci. 1997 Jan 1;17(1):477-92
references: 8987772
references: Life Sci. 1979 Dec 3;25(23):1957-62
references: 160969
references: Brain Res Bull. 1983 Jun;10(6):735-9
references: 6311357
references: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1275-80
references: 10655521
references: Acta Physiol Scand. 1995 Jun;154(2):165-76
references: 7572212
references: Neuroendocrinology. 1996 Aug;64(2):114-23
references: 8857605
references: Neuron. 2001 Apr;30(1):37-50
references: 11343643
references: J Neurosci. 2010 Mar 31;30(13):4735-45
references: 20357124
references: Biochim Biophys Acta. 2010 Oct;1800(10):1056-67
references: 20100545
references: J Neurosci. 2011 Apr 27;31(17):6392-7
references: 21525279
references: Behav Brain Res. 1998 Jun;93(1-2):185-90
references: 9659999
references: Trends Neurosci. 2003 Jan;26(1):17-22
references: 12495858
references: J Physiol. 1993 Oct;470:539-58
references: 8308742
references: Neurosci Biobehav Rev. 2005 Jan;28(8):811-25
references: 15642623
references: Annu Rev Pharmacol Toxicol. 1988;28:285-310
references: 2898236
references: Epilepsy Res. 1989 May-Jun;3(3):191-8
references: 2731518
references: Brain Res. 2011 Mar 16;1379:71-85
references: 20828542
references: Neuroscience. 2013 Jun 3;239:3-16
references: 23103216
references: Exp Neurol. 2009 Sep;219(1):319-27
references: 19505458
references: J Clin Invest. 2009 Jan;119(1):99-109
references: 19104150
references: Brain Res Rev. 2007 Oct;55(2):343-55
references: 17395265
references: J Pharmacol Exp Ther. 1998 Mar;284(3):1147-55
references: 9495877
references: Endocrinology. 2013 Feb;154(2):819-30
references: 23183182
references: Brain Res. 1989 Feb 6;479(1):115-9
references: 2466534