Rapid elevations in limbic endocannabinoid content by glucocorticoid hormones in vivo.
Functional interactions between glucocorticoids and the endocannabinoid system have been repeatedly documented; yet, to date, no studies have demonstrated in vivo that glucocorticoid hormones regulate endocannabinoid signaling. We demonstrate that systemic administration of the glucocorticoid corticosterone (3 and 10 mg/kg) resulted in an increase in the tissue content of the endocannabinoid N-arachidonylethanolamine (AEA) within several limbic structures (amygdala, hippocampus, hypothalamus), but not the prefrontal cortex, of male rats. Tissue AEA content was increased at 10min and returned to control 1h post-corticosterone administration. The other primary endocannabinoid, 2-arachidonoylglycerol, was found to be elevated by corticosterone exclusively within the hypothalamus. The rapidity of the change suggests that glucocorticoids act through a non-genomic pathway. Tissue contents of two other N-acylethanolamines, palmitoylethanolamide and oleolyethanolamide, were not affected by corticosterone treatment, suggesting that the mechanism of regulation is neither fatty acid amide nor N-acylphosphatidylethanolamine phospholipase D. These data provide in vivo support for non-genomic steroid effects in mammals and suggest that AEA is a mediator of these effects.
Hill
Matthew N
MN
Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA. mhill@rockefeller.edu
Karatsoreos
Ilia N
IN
Hillard
Cecilia J
CJ
McEwen
Bruce S
BS
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage / Q000494:pharmacology; D063388:Endocannabinoids; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005938:Glucocorticoids; D006728:Hormones; D003345:Corticosterone
J Biol Chem. 2006 Sep 8;281(36):26465-72
16818490
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9371-6
11470906
Horm Behav. 1994 Dec;28(4):396-405
7729808
Science. 1991 Jun 28;252(5014):1848-51
2063198
Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4579-80
19293387
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19204-7
16361444
J Neurosci Res. 2006 Nov 15;84(7):1580-7
16998919
Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4888-93
19255436
J Neurosci. 2006 Jun 14;26(24):6643-50
16775153
J Lipid Res. 2005 Feb;46(2):342-9
15576840
Endocrinology. 2007 Feb;148(2):493-500
17095597
Front Neuroendocrinol. 2008 May;29(2):273-91
18054070
J Neurosci. 2003 Jun 15;23(12):4850-7
12832507
J Biol Chem. 2008 Apr 4;283(14):9341-9
18227059
Physiol Rev. 2003 Jul;83(3):1017-66
12843414
Prog Brain Res. 2008;167:79-97
18037008
Chem Rev. 2008 May;108(5):1687-707
18429637
Endocrinology. 2006 Dec;147(12):5549-56
16946006