This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Droste, S. K. Articles by Linthorst, A. C. E. Search for Related Content PubMed PubMed Citation Articles by Droste, S. K. Articles by Linthorst, A. C. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Stress

Corticosterone Levels in the Brain Show a Distinct Ultradian Rhythm but a Delayed Response to Forced Swim Stress

Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, United Kingdom

Address all correspondence and requests for reprints to: Dr. Astrid C. E. Linthorst, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Clinical Science South Bristol, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom. E-mail: astrid.linthorst{at}bristol.ac.uk.

Circulating corticosterone levels show an ultradian rhythm resulting from the pulsatile release of glucocorticoid hormone by the adrenal cortex. Because the pattern of hormone availability to corticosteroid receptors is of functional significance, it is important to determine whether there is also a pulsatile pattern of corticosterone concentration within target tissues such as the brain. Furthermore, it is unclear whether measurements of plasma corticosterone levels accurately reflect corticosterone levels in the brain. Given that the hippocampus is a principal site of glucocorticoid action, we investigated in male rats hippocampal extracellular corticosterone concentrations under baseline and stress conditions using rapid-sampling in vivo microdialysis. We found that hippocampal extracellular corticosterone concentrations show a distinct circadian and ultradian rhythm. The PULSAR algorithm revealed that the pulse frequency of hippocampal corticosterone is 1.03 ± 0.07 pulses/h between 0900 and 1500 h and is significantly higher between 1500 and 2100 h (1.31 ± 0.05). The hippocampal corticosterone response to stress is stressor dependent but resumes a normal ultradian pattern rapidly after the termination of the stress response. Similar observations were made in the caudate putamen. Importantly, simultaneous measurements of plasma and hippocampal glucocorticoid levels showed that under stress conditions corticosterone in the brain peaks 20 min later than in plasma but clears concurrently, resulting in a smaller exposure of the brain to stress-induced hormone than would be predicted by plasma hormone concentrations. These data are the first to demonstrate that the ultradian rhythm of corticosterone is maintained over the blood-brain barrier and that tissue responses cannot be reliably predicted from the measurement of plasma corticosterone levels.

This article has been cited by other articles:

				J. D. Veldhuis, F. Roelfsema, A. Iranmanesh, B. J. Carroll, D. M. Keenan, and S. M. Pincus Basal, Pulsatile, Entropic (Patterned), and Spiky (Staccato-like) Properties of ACTH Secretion: Impact of Age, Gender, and Body Mass Index J. Clin. Endocrinol. Metab., October 1, 2009; 94(10): 4045 - 4052. [Abstract] [Full Text] [PDF]

				S. K. Droste, A. Collins, S. L. Lightman, A. C. E. Linthorst, and J. M. H. M. Reul Distinct, Time-Dependent Effects of Voluntary Exercise on Circadian and Ultradian Rhythms and Stress Responses of Free Corticosterone in the Rat Hippocampus Endocrinology, September 1, 2009; 150(9): 4170 - 4179. [Abstract] [Full Text] [PDF]

				E. M. Prager and L. R. Johnson Stress at the Synapse: Signal Transduction Mechanisms of Adrenal Steroids at Neuronal Membranes Sci. Signal., September 1, 2009; 2(86): re5 - re5. [Abstract] [Full Text] [PDF]

				K. L. Schmidt, E. H. Chin, A. H. Shah, and K. K. Soma Cortisol and corticosterone in immune organs and brain of European starlings: developmental changes, effects of restraint stress, comparison with zebra finches Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R42 - R51. [Abstract] [Full Text] [PDF]

				E. R. de Kloet and R. A. Sarabdjitsingh Everything Has Rhythm: Focus on Glucocorticoid Pulsatility Endocrinology, July 1, 2008; 149(7): 3241 - 3243. [Full Text] [PDF]