Abstract
Previous studies suggest that circulating glucocorticoids may influence the encoding and processing of sensory stimuli. The current study investigated this hypothesis by measuring the generation (amplitude), gating (recovery cycle), and sensitivity (intensity function) of auditory evoked responses in C57BL/6 mice treated with chronic corticosterone (0, 1, 5, 15, or 30 mg/kg/day for 14 days). We found that low-dose corticosterone (5 but not 1 mg/kg/day) enhanced the amplitude and improved gating of evoked potentials without affecting the intensity function. In comparison, higher doses (15 and 30 mg/kg/day) decreased the amplitude and impaired gating of evoked potentials, also without altering the stimulus intensity function. At all doses, lower amplitudes of evoked potentials were significantly correlated with higher circulating corticosterone levels. These data highlight the need to consider serum glucocorticoid levels when assessing human disease states associated with aberrations of information processing such as schizophrenia and depression.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Adler LE, Rose G, Freedman R (1986). Neurophysiological studies of sensory gating in rats: effects of amphetamine, phencyclidine, and haloperidol. Biol Psychiatry 21: 787–798.
Arborelius L, Skelton KH, Thrivikraman KV, Plotsky PM, Schulz DW, Owens MJ (2000). Chronic administration of the selective corticotropin-releasing factor 1 receptor antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the rat. J Pharmacol Exp Ther 294: 588–597.
Ashton CH, Lunn B, Marsh VR, Young AH (2000). Subchronic hydrocortisone treatment alters auditory evoked potentials in normal subjects. Psychopharmacology (Berl) 152: 87–92.
Born J, Hitzler V, Pietrowsky R, Pauschinger P, Fehm HL (1989). Influences of cortisol on auditory evoked potentials (AEPs) and mood in humans. Neuropsychobiology 20: 145–151.
Boutros N, Nasrallah H, Leighty R, Torello M, Tueting P, Olson S (1997). Auditory evoked potentials, clinical vs research applications. Psychiatry Res 69: 183–195.
Budd TW, Barry RJ, Gordon E, Rennie C, Michie PT (1998). Decrement of the N1 auditory event-related potential with stimulus repetition: habituation vs refractoriness. Int J Psychophysiol 31: 51–68.
Connolly PM, Maxwell C, Liang Y, Kahn JB, Kanes SJ, Abel T et al (2004). The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components. Neurochem Res 29: 1179–1188.
Connolly PM, Maxwell CR, Kanes SJ, Abel T, Liang Y, Tokarczyk J et al (2003). Inhibition of auditory evoked potentials and prepulse inhibition of startle in DBA/2J and DBA/2Hsd inbred mouse substrains. Brain Res 992: 85–95.
DeKrey GK, Kerkvliet NI (1995). Effects of exogenous corticosterone treatment on alloantigen-specific cytotoxic T lymphocyte activity in mice. J Pharmacol Exp Ther 273: 823–829.
Ehlers CL, Somes C (2002). Long latency event-related potentials in mice: effects of stimulus characteristics and strain. Brain Res 957: 117–128.
Erway LC, Willott JF, Archer JR, Harrison DE (1993). Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains. Hear Res 65: 125–132.
Erwin RJ, Shtasel D, Gur RE (1994). Effects of medication history on midlatency auditory evoked responses in schizophrenia. Schizophr Res 11: 251–258.
Frankel WN, Beyer B, Maxwell CR, Pretel S, Letts VA, Siegel SJ (2005). Development of a new genetic model for absence epilepsy: spike-wave seizures in C3H/He and backcross mice. J Neurosci 25: 3452–3458.
Glass GV, McGaw B, Smith ML (1981). Meta-Analysis in Social Research. Sage: Newbury Park, CA.
Halford JJ (2003). Neurophysiologic correlates of psychiatric disorders and potential applications in epilepsy. Epilepsy Behav 4: 375–385.
Hall RC, Popkin MK, Stickney SK, Gardner ER (1979). Presentation of the steroid psychoses. J Nerv Ment Dis 167: 229–236.
Hegerl U, Gallinat J, Juckel G (2001). Event-related potentials. Do they reflect central serotonergic neurotransmission and do they predict clinical response to serotonin agonists? J Affect Disord 62: 93–100.
Janowsky DS, Risch C (1979). Amphetamine psychosis and psychotic symptoms. Psychopharmacology (Berl) 65: 73–77.
Javitt DC, Jayachandra M, Lindsley RW, Specht CM, Schroeder CE (2000). Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP). Clin Neurophysiol 111: 833–836.
Jin Y, Potkin SG, Patterson JV, Sandman CA, Hetrick WP, Bunney Jr WE (1997). Effects of P50 temporal variability on sensory gating in schizophrenia. Psychiatry Res 70: 71–81.
Knight RT, Brailowsky S, Scabini D, Simpson GV (1985). Surface auditory evoked potentials in the unrestrained rat: component definition. Electroencephalogr Clin Neurophysiol 61: 430–439.
LaBossiere E, Glickstein M (1976). Histological Processing for the Neural Science. Charles C Thomas: Springfield.
Liang Y, Trief D, Maxwell CR, Majumdar SM, Majewski-Tiedeken C, Kanes SJ et al (2004). Inbred Strains Vary for Effects of Acute Ketamine. Society for Neuroscience: Washington, DC.
Light GA, Braff DL (1999). Human and animal studies of schizophrenia-related gating deficits. Curr Psychiatry Rep 1: 31–40.
Man MS, Young AH, McAllister-Williams RH (2002). Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice. J Psychopharmacol 16: 245–252.
Maxwell CR, Kanes SJ, Abel T, Siegel SJ (2004a). Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications. Neuroscience 129: 101–107.
Maxwell CR, Liang Y, Weightman BD, Kanes SJ, Abel T, Gur RE et al (2004b). Effects of chronic olanzapine and haloperidol differ on the mouse N1 auditory evoked potential. Neuropsychopharmacology 29: 739–746.
McAllister-Williams RH, Rugg MD (2002). Effects of repeated cortisol administration on brain potential correlates of episodic memory retrieval. Psychopharmacology (Berl) 160: 74–83.
Miller AH, Spencer RL, Stein M, McEwen BS (1990). Adrenal steroid receptor binding in spleen and thymus after stress or dexamethasone. Am J Physiol 259: E405–E412.
Morton NM, Ramage L, Seckl JR (2004). Down-regulation of adipose 11beta-hydroxysteroid dehydrogenase type 1 by high-fat feeding in mice: a potential adaptive mechanism counteracting metabolic disease. Endocrinology 145: 2707–2712.
Muck-Seler D, Pivac N, Mustapic M, Crncevic Z, Jakovljevic M, Sagud M (2004). Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. Psychiatry Res 127: 217–226.
Nemeroff C (2004). Early-life adversity, CRF dysregulation, and vulnerability to mood and anxiety disorders. Psychopharmacol Bull 38: 14–20.
Ninomiya H, Sato E, Onitsuka T, Hayashida T, Tashiro N (2000). Auditory P50 obtained with a repetitive stimulus paradigm shows suppression to high-intensity tones. Psychiatry Clin Neurosci 54: 493–497.
Ogura C, Nageishi Y, Matsubayashi M, Omura F, Kishimoto A, Shimokochi M (1991). Abnormalities in event-related potentials, N100, P200, P300 and slow wave in schizophrenia. Jpn J Psychiatry Neurol 45: 57–65.
Pincze Z, Lakatos P, Rajkai C, Ulbert I, Karmos G (2001). Separation of mismatch negativity and the N1 wave in the auditory cortex of the cat: a topographic study. Clin Neurophysiol 112: 778–784.
Seckl JR (1997). 11beta-hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action? Front Neuroendocrinol 18: 49–99.
Shelley AM, Silipo G, Javitt DC (1999). Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction. Schizophr Res 37: 65–79.
Siegel SJ, Connolly P, Liang Y, Lenox RH, Gur RE, Bilker WB et al (2003). Effects of strain, novelty, and NMDA blockade on auditory-evoked potentials in mice. Neuropsychopharmacology 28: 675–682.
Siegel SJ, Maxwell CR, Majumdar S, Trief DF, Lerman C, Gur RE et al (2005). Monoamine reuptake inhibition and nicotine receptor antagonism reduce amplitude and gating of auditory evoked potentials. Neuroscience 133: 729–738.
Siegel SJ, Winey KI, Gur RE, Lenox RH, Bilker WB, Ikeda D et al (2002). Surgically implantable long-term antipsychotic delivery systems for the treatment of schizophrenia. Neuropsychopharmacology 26: 817–823.
Stevens KE, Bullock AE, Collins AC (2001). Chronic corticosterone treatment alters sensory gating in C3H mice. Pharmacol Biochem Behav 69: 359–366.
Stevens KE, Kem WR, Freedman R (1999). Selective alpha 7 nicotinic receptor stimulation normalizes chronic cocaine-induced loss of hippocampal sensory inhibition in C3H mice. Biol Psychiatry 46: 1443–1450.
Tabares-Seisdedos R, Balanza-Martinez V, Pallardo Y, Salazar-Fraile J, Selva G, Vilela C et al (2001). Similar effect of family history of psychosis on Sylvian fissure size and auditory P200 amplitude in schizophrenic and bipolar subjects. Psychiatry Res 108: 29–38.
Umbricht D, Vyssotky D, Latanov A, Nitsch R, Brambilla R, D'Adamo P et al (2004). Midlatency auditory event-related potentials in mice: comparison to midlatency auditory ERPs in humans. Brain Res 1019: 189–200.
Vandoolaeghe E, van Hunsel F, Nuyten D, Maes M (1998). Auditory event related potentials in major depression: prolonged P300 latency and increased P200 amplitude. J Affect Disord 48: 105–113.
Willott JF, Carlson S (1995). Modification of the acoustic startle response in hearing-impaired C57BL/6J mice: prepulse augmentation and prolongation of prepulse inhibition. Behav Neurosci 109: 396–403.
Zheng QY, Johnson KR, Erway LC (1999). Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 130: 94–107.
Acknowledgements
This work was supported by Eli Lilly and Co. (SJS), P50 MH 6404501 (SJS, TA, SJK) and The Stanley Medical Research Institute (SJS). We thank Dr Irwin Lucki, Dr Rita Valentino, Dr Karen Stevens, and Dr Raquel Gur for helpful comments and discussions during the formulation of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maxwell, C., Ehrlichman, R., Liang, Y. et al. Corticosterone Modulates Auditory Gating in Mouse. Neuropsychopharmacol 31, 897–903 (2006). https://doi.org/10.1038/sj.npp.1300879
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.npp.1300879
Keywords
This article is cited by
-
BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects
Nature Communications (2021)


