Differential MR/GR activation in mice results in emotional states beneficial or impairing for cognition.
Corticosteroids regulate stress response and influence emotion, learning, and memory via two receptors in the brain, the high-affinity mineralocorticoid (MR) and low-affinity glucocorticoid receptor (GR). We test the hypothesis that MR- and GR-mediated effects interact in emotion and cognition when a novel situation is encountered that is relevant for a learning process. By adrenalectomy and additional constant corticosterone supplement we obtained four groups of male C57BL/6J mice with differential chronic MR and GR activations. Using a hole board task, we found that mice with continuous predominant MR and moderate GR activations were fast learners that displayed low anxiety and arousal together with high directed explorative behavior. Progressive corticosterone concentrations with predominant action via GR induced strong emotional arousal at the expense of cognitive performance. These findings underline the importance of a balanced MR/GR system for emotional and cognitive functioning that is critical for mental health.
Brinks
Vera
V
Gorlaeus Lab, Division of Medical Pharmacology, LACDR/LUMC, Leiden University, Einsteinweg 55, 2300 Leiden, The Netherlands.
van der Mark
Maaike H
MH
de Kloet
E Ron
ER
Oitzl
Melly S
MS
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000315:Adrenalectomy; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000097:blood / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000819:agonists / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003345:Corticosterone
Biol Psychiatry. 1999 Nov 1;46(9):1140-52
10560021
Anat Rec. 1958 Nov;132(3):281-95
13637404
Eur J Pharmacol. 2000 Sep 29;405(1-3):397-406
11033344
J Psychiatr Res. 2000 Nov-Dec;34(6):383-92
11165305
Neuroendocrinology. 2001 Apr;73(4):261-71
11340340
Mol Endocrinol. 2005 Feb;19(2):441-58
15514029
Behav Brain Res. 2005 Nov 7;164(2):197-205
16107281
Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1787-97
16141309
Acta Psychiatr Scand. 2005 Dec;112(6):434-41
16279872
Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):195-200
16368758
Neurosci Lett. 2006 Mar 20;396(1):12-6
16326007
Behav Neurosci. 2006 Feb;120(1):60-71
16492117
Handb Exp Pharmacol. 2005;(169):205-23
16594260
Trends Pharmacol Sci. 2006 May;27(5):244-50
16584791
J Psychiatr Res. 2001 May-Jun;35(3):147-54
11461710
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12790-5
11606764
Psychosom Med. 2001 Nov-Dec;63(6):985-93
11719638
Nat Genet. 2002 Aug;31(4):363-9
12091910
Stress. 2002 Feb;5(1):73-9
12171770
Eur J Neurosci. 2003 Jan;17(1):128-36
12534976
Eur J Neurosci. 2003 May;17(9):1928-34
12752792
Brain Cogn. 2003 Jun;52(1):4-14
12812799
Behav Neurosci. 2006 Apr;120(2):249-56
16719689
J Nerv Ment Dis. 2006 Jul;194(7):478-84
16840843
Behav Brain Res. 2006 Sep 25;172(2):324-32
16814878
Neurobiol Learn Mem. 2006 Sep;86(2):150-9
16580234
Biol Psychiatry. 2006 Sep 1;60(5):472-8
16483550
Nat Neurosci. 2003 Oct;6(10):1100-7
12973355
BMC Physiol. 2003 Jun 9;3:4
12795810
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Dec;27(8):1213-23
14659476
Biol Psychiatry. 2004 Apr 1;55(7):715-23
15039000
Neural Plast. 2003;10(4):327-33
15152986
J Steroid Biochem Mol Biol. 1990 Nov 20;37(3):387-94
2257242
Behav Neurosci. 1992 Feb;106(1):62-71
1313244
Physiol Behav. 1992 Aug;52(2):355-61
1355919
J Neurosci. 1993 Sep;13(9):3839-47
8396170
Eur J Neurosci. 1994 Jul 1;6(7):1072-9
7952288
Eur J Neurosci. 1994 Aug 1;6(8):1292-7
7981871
Brain Res. 1994 Sep 19;657(1-2):227-35
7820622
J Neurosci. 1995 Jan;15(1 Pt 1):61-9
7823152
Psychoneuroendocrinology. 1995;20(4):385-94
8532822
Pharmacol Biochem Behav. 1996 May;54(1):261-7
8728567
Pharmacol Biochem Behav. 1997 Mar;56(3):507-13
9077590
Brain Res. 1997 Mar 28;752(1-2):127-35
9106448
Psychoneuroendocrinology. 1996 Nov;21(8):681-93
9247987
Eur J Neurosci. 1997 Nov;9(11):2284-96
9464923
Physiol Behav. 1998 Mar;63(5):933-7
9618019
Endocrinology. 1999 Jan;140(1):310-7
9886840
Nat Genet. 1999 Sep;23(1):99-103
10471508
Trends Neurosci. 1999 Oct;22(10):422-6
10481183
J Neurosci. 2000 May 15;20(10):3843-52
10804224