title: Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats.
abstract: Intranasal administration has been widely used to investigate the effects of the neuropeptides vasopressin and oxytocin on human behaviour and neurological disorders, although exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. In the present study, we investigated whether the intranasal administration of vasopressin and oxytocin to rats induces the expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally-administered peptide, whether it alters neuronal activity in the way that centrally-administered peptide does, and whether it affects behaviour in the ways that are expected from studies of centrally-administered peptide. We found that, whereas i.c.v. injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. By contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data obtained in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behaviour in the ways described for central administration of the peptides.
authors: Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK. mike.ludwig@ed.ac.uk
authors: M
authors: M
authors: Ludwig
authors: V A
authors: VA
authors: Tobin
authors: M F
authors: MF
authors: Callahan
authors: E
authors: E
authors: Papadaki
authors: A
authors: A
authors: Becker
authors: M
authors: M
authors: Engelmann
authors: G
authors: G
authors: Leng
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014667:Vasopressins
references: Neuroscience. 1993 Apr;53(3):735-48
references: 8487952
references: Acta Endocrinol (Copenh). 1987 Jul;115(3):307-12
references: 3618082
references: Allergy Asthma Proc. 1996 Jul-Aug;17(4):179-84
references: 8871735
references: Neuroscience. 2004;127(2):481-96
references: 15262337
references: Science. 2008 Nov 7;322(5903):900-4
references: 18988842
references: Ann N Y Acad Sci. 1969 Jul 30;159(3):852-9
references: 5260302
references: Neuroscience. 2001;105(2):479-88
references: 11672613
references: Horm Behav. 2012 Mar;61(3):392-9
references: 22197271
references: Nature. 2010 Mar 18;464(7287):413-7
references: 20182426
references: Neuron. 2010 Mar 25;65(6):768-79
references: 20346754
references: Am J Obstet Gynecol. 1971 Jul 15;110(6):788-94
references: 5562001
references: Am J Obstet Gynecol. 1958 Jul;76(1):103-7
references: 13545285
references: Pharm Res. 1992 Jan;9(1):1-9
references: 1589391
references: J Histochem Cytochem. 2000 Sep;48(9):1215-22
references: 10950878
references: Clin Pharmacokinet. 2001;40(12):907-46
references: 11735609
references: Nature. 1983 Jul 14-20;304(5922):163-4
references: 6866111
references: Trends Neurosci. 2012 Nov;35(11):649-59
references: 22974560
references: Prog Brain Res. 1998;119:321-34
references: 10074797
references: Neuropathol Appl Neurobiol. 1995 Jun;21(3):175-80
references: 7477724
references: Pharm Res. 2003 Aug;20(8):1225-30
references: 12948020
references: Am J Physiol. 1994 Feb;266(2 Pt 2):R592-8
references: 8141420
references: Nat Neurosci. 2004 Oct;7(10):1048-54
references: 15452576
references: Front Neuroendocrinol. 2009 Oct;30(4):548-557
references: 19505497
references: BMC Neurosci. 2008 Dec 10;9 Suppl 3:S5
references: 19091002
references: J Neurosci. 2004 Mar 24;24(12):2974-82
references: 15044536
references: Neurosci Lett. 1987 Jun 26;77(3):353-9
references: 3614767
references: Brain Res Mol Brain Res. 1990 Feb;7(2):131-7
references: 2160040
references: Mol Cell Neurosci. 1993 Feb;4(1):93-106
references: 19912912
references: Biol Psychiatry. 2013 Aug 1;74(3):180-8
references: 23079235
references: Pharm Res. 2005 Jul;22(7):1121-8
references: 16028013
references: Regul Pept. 2005 Dec 15;132(1-3):107-12
references: 16213606
references: J Neurosci. 1996 Oct 1;16(19):6319-29
references: 8815911
references: Eur J Pharmacol. 1985 Jun 7;112(2):203-10
references: 4029259
references: Peptides. 1998;19(6):999-1005
references: 9700747
references: Eur J Pharmacol. 1999 Jul 2;376(1-2):45-51
references: 10440088
references: Prog Brain Res. 2008;170:3-15
references: 18655867
references: Br Med J. 1961 Mar 11;1(5227):709-11
references: 13716907
references: Eur J Neurosci. 1995 Apr 1;7(4):592-8
references: 7620610
references: Brain Res. 1999 Apr 17;825(1-2):115-31
references: 10216179
references: J Physiol. 1959 Dec;149:586-92
references: 14417730
references: Brain Res. 1983 Feb 28;262(1):143-9
references: 6831225
references: Neurosci Biobehav Rev. 2001 May;25(3):275-86
references: 11378181
references: Physiol Behav. 1994 Jan;55(1):145-9
references: 8140159
references: Am J Obstet Gynecol. 1960 Apr;79:780-8
references: 14401010
references: Nat Neurosci. 2002 Jun;5(6):514-6
references: 11992114
references: Endocrinology. 2001 Apr;142(4):1659-68
references: 11250948
references: Eur J Neurosci. 1997 Dec;9(12):2532-40
references: 9517458
references: Nature. 1981 Jun 11;291(5815):491-3
references: 7231561
references: Nat Protoc. 2011 Jul 14;6(8):1152-62
references: 21799485
references: Neurosci Res. 2006 Apr;54(4):269-75
references: 16427151
references: Cell Tissue Res. 2011 May;344(2):227-37
references: 21437658
references: Exp Clin Endocrinol. 1985 Apr;85(2):245-8
references: 4018162
references: Psychoneuroendocrinology. 2011 Sep;36(8):1114-26
references: 21429671
references: Drugs. 1992 Aug;44(2):216-24
references: 1382016
references: J Pharmacol. 1985;16 Suppl 2:51-68
references: 2867253
references: Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):959-65
references: 17698297
references: Eur J Neurosci. 2004 Aug;20(3):658-70
references: 15255977
references: Nature. 1984 Mar 15-21;308(5956):276-8
references: 6322010
references: J Neuroendocrinol. 2012 Apr;24(4):599-608
references: 21981277
references: J Cereb Blood Flow Metab. 1985 Sep;5(3):350-7
references: 3897253
references: Acta Neurobiol Exp (Wars). 2001;61(4):267-76
references: 11905148
references: Psychopharmacology (Berl). 1987;91(3):363-8
references: 3104959
references: Neurosci Biobehav Rev. 1996 Autumn;20(3):341-58
references: 8880728
references: Neuropharmacology. 2012 Jan;62(1):398-405
references: 21871467
references: B-ENT. 2009;5 Suppl 13:21-37
references: 20084803
references: Neuropsychopharmacology. 2012 May;37(6):1323-37
references: 22278093
references: Horm Behav. 2012 Mar;61(3):410-8
references: 22265852
references: J Drug Target. 2002 Jun;10(4):285-96
references: 12164377
references: Physiol Behav. 1998 Jun 15;64(4):543-7
references: 9761230
references: Nat Rev Neurosci. 2011 Aug 19;12(9):524-38
references: 21852800
references: J Neuroimmunol. 2004 Jun;151(1-2):66-77
references: 15145605
references: J Neurosci. 1998 Mar 1;18(5):1879-85
references: 9465012