Skip to main content
SpringerLink
Log in

Glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Cortisol levels rise sharply immediately after electroconvulsive therapy (ECT); the resultant stimulation of steroid receptors in the hippocampus may be beneficial or harmful to cognition, depending on the magnitude of the stimulation. Steroid mechanisms may therefore modulate ECT-induced amnesia.

Objectives

Using mifepristone (a glucocorticoid receptor antagonist) as a chemical probe, we sought to examine steroid mechanisms in an animal model of ECT-induced retrograde amnesia.

Materials and methods

Adult, male Wistar rats (n = 68) trained in a step-through passive-avoidance task were randomized to receive mifepristone (20 or 40 mg kg−1 day−1) or vehicle (control). These treatments were administered 1 day before the electroconvulsive shock (ECS) course and, again, 1 h before each of five once-daily true (30 mC) or sham ECS. Recall of pre-ECS learning was tested 1 day after the last ECS.

Results

Relative to sham ECS, true ECS resulted in significant retrograde amnesia in the vehicle group but not in either of the mifepristone groups. In sham ECS-treated animals, mifepristone did not significantly influence recall. In ECS-treated rats, the higher but not the lower dose of mifepristone was associated with significant protection against the retrograde amnesia evident in the vehicle group.

Conclusion

Mifepristone administered before the ECT seizure may attenuate ECT-induced retrograde amnesia. This suggests that glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abrams R (1988) Electroconvulsive therapy. Oxford University Press, New York

    Google Scholar 

  • Agarwai MK (1996) The antiglucocorticoid action of mifepristone. Pharmacol Ther 70:183–213

    Article  PubMed  CAS  Google Scholar 

  • Anand A, Andrade C, Sudha C, Guido S, Venkataraman BV (2001) Phenylephrine and ECS-induced retrograde amnesia. J ECT 17:166–169

    Article  PubMed  CAS  Google Scholar 

  • Andrade C (1992) The mechanism of action of ECT. In: Gangadhar BN (ed) Proceedings of the national workshop on ECT: priorities for research and practice in India, NIMHANS, Bangalore, pp 107–130

  • Andrade C (2005) Electroconvulsive therapy. In: Bhugra D, Ranjith G, Patel V (eds) Handbook of psychiatry: a South Asian perspective. Byword Publishers, New Delhi, pp 553–568

    Google Scholar 

  • Andrade C, Thyagarajan S, Vinod PS, Srikanth SN, Rao NSK, Chandra JS (2002a) Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats. J ECT 18:197–202

    Article  PubMed  Google Scholar 

  • Andrade C, Kurinji S, Sudha S, Chandra JS (2002b) Effects of pulse amplitude, pulse frequency, and stimulus duration on seizure threshold: a laboratory investigation. J ECT 18:144–148

    Article  PubMed  Google Scholar 

  • Aperia B, Bergman H, Engelbrektson K, Thoren M, Wetterberg L (1985) Effects of electroconvulsive therapy on neuropsychological function and circulating levels of ACTH, cortisol, prolactin, and TSH in patients with major depressive illness. Acta Psychiatr Scand 72:536–541

    Article  PubMed  CAS  Google Scholar 

  • Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu E-E, Schold C, Schatzberg AF (2002) An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 52:386–392

    Article  PubMed  CAS  Google Scholar 

  • Borowicz KK, Luszczki J, Swiader M, Kleinrok Z, Czuczwar SJ (2004) Influence of sexual hormone antagonists on the anticonvulsant action of conventional antiepileptic drugs against electrically- and pentylenetetrazol-induced seizures in mice. Eur Neuropsychopharmacol 14:77–85

    Article  PubMed  CAS  Google Scholar 

  • Capasso A, Casciano C, Loizzo A (2002) Dexamethasone reduces morphine-induced Straub reaction in mice. J Pharm Pharmacol 54:983–987

    Article  PubMed  CAS  Google Scholar 

  • de Kloet ER, Oitzl MS, Joels M (1999) Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci 22:422–426

    Article  PubMed  Google Scholar 

  • Erickson K, Drevets W, Schulkin J (2003) Glucocorticoid regulation of diverse cognitive functions in normal and pathological emotional states. Neurosci Biobehav Rev 27:233–246

    Article  PubMed  CAS  Google Scholar 

  • Gold PW, Drevets WC, Charney DS (2002) New insights into the role of cortisol and the glucocorticoid receptor in severe depression. Biol Psychiatry 52:381–385

    Article  PubMed  CAS  Google Scholar 

  • Heffelfinger AK, Newcomer JW (2001) Glucocorticoid effects on memory function over the human life span. Dev Psychopathol 13:491–513

    Article  PubMed  CAS  Google Scholar 

  • Heikinheimo O, Pesonen U, Huupponen R, Koulu M, Lahteenmaki P (1994) Hepatic metabolism and distribution of mifepristone and its metabolites in rats. Hum Reprod 9(Suppl 1):40–46

    PubMed  CAS  Google Scholar 

  • Kamath S, Andrade C, Faruqi S, Venkataraman BV, Naga Rani MA, Candade VS (1997) Evaluation of pre-ECS antihypertensive drug administration in the attenuation of ECS-induced amnesia in rats. Convuls Ther 13:185–195

    PubMed  CAS  Google Scholar 

  • Koenig HN, Olive MF (2004) The glucocorticoid receptor antagonist mifepristone reduces ethanol intake in rats under limited access conditions. Psychoneuroendocrinology 29:999–1003

    Article  PubMed  CAS  Google Scholar 

  • Korte SM, de Boer SF, de Kloet ER, Bohus B (1995) Anxiolytic-like effects of selective mineralocorticoid and glucocorticoid antagonists on fear-enhanced behavior in the elevated plus-maze. Psychoneuroendocrinology 20:385–394

    Article  PubMed  CAS  Google Scholar 

  • Kronfol Z, Hamdan-Allen G, Goel K, Hill EM (1991) Effects of single and repeated electroconvulsive therapy sessions on plasma ACTH, prolactin, growth hormone and cortisol concentrations. Psychoneuroendocrinology 16:345–352

    Article  PubMed  CAS  Google Scholar 

  • Lerer B (1985) Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium. Biol Psychiatry 20:20–40

    Article  PubMed  CAS  Google Scholar 

  • Lerer B, Stanley M, McIntyre I, Altman H (1984) Electroconvulsive shock and brain muscarinic receptors: relationship to anterograde amnesia. Life Sci 35:2659–2664

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, Lepage M (2001) Stress, memory, and the hippocampus: can’t live with it, can’t live without it. Behav Brain Res 127:137–158

    Article  PubMed  CAS  Google Scholar 

  • McCullers DL, Sullivan PG, Scheff SW, Herman JP (2002) Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat. Neuroscience 109:219–230

    Article  PubMed  CAS  Google Scholar 

  • McDaniel WW, Sahota AK, Vyas BV, Laguerta N, Hategan L, Oswald J (2006) Ketamine appears associated with better word recall than etomidate after a course of 6 electroconvulsive therapies. J ECT 22:103–106

    Article  PubMed  CAS  Google Scholar 

  • Neylan TC, Canick JD, Hall SE, Reus VI, Sapolsky RM, Wolkowitz OM (2001) Cortisol levels predict cognitive impairment induced by electroconvulsive therapy. Biol Psychiatry 50:331–336

    Article  PubMed  CAS  Google Scholar 

  • Oitzl MS, Fluttert M, Sutanto W, de Kloet ER (1998a) Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats. Eur J Neurosci 10:3759–3766

    Article  PubMed  CAS  Google Scholar 

  • Oitzl MS, Fluttert M, de Kloet ER (1998b) Acute blockade of hippocampal glucocorticoid receptors facilitates spatial learning in rats. Brain Res 797:159–162

    Article  PubMed  CAS  Google Scholar 

  • Rao NSK, Andrade C, Reddy KP, Madappa KN, Thyagarajan S, Chandra JS (2002) Memory protective effect of indomethacin against electroconvulsive shocks induced by retrograde amnesia in rats. Biol Psychiatry 51:770–773

    Article  PubMed  CAS  Google Scholar 

  • Sackeim HA (1992) The cognitive effects of electroconvulsive therapy. In: Thal LJ, Moos WH, Gamzu ER (eds) Cognitive disorders: pathophysiology and treatment. Marcel Dekker, New York, pp 183–228

    Google Scholar 

  • Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, Fitzsimons L, Moody BJ, Clark J (2000) A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry 57:425–434

    Article  PubMed  CAS  Google Scholar 

  • Sousa N, Almeida OF (2002) Corticosteroids: sculptors of the hippocampal formation. Rev Neurosci 13:59–84

    PubMed  CAS  Google Scholar 

  • Stewart CA, Reid IC (1994) Ketamine prevents ECS-induced synaptic enhancement in rat hippocampus. Neurosci Lett 178:11–14. Erratum in: Neurosci Lett 1996; 210:218

    Google Scholar 

  • Sudha S, Andrade C, Anand A, Guido S, Venkataraman BV (2001) Nitroprusside and ECS-induced retrograde amnesia. J ECT 17:41–44

    Article  PubMed  CAS  Google Scholar 

  • Vinekar AS, Andrade C, Sriprada VT, George J, Joseph T, Chandra JS (1998) Attenuation of ECS-induced retrograde amnesia by using an herbal formulation. J ECT 14:83–88

    PubMed  CAS  Google Scholar 

  • Weizman A, Gil-Ad I, Grupper D, Tyano S, Laron Z (1987) The effect of acute and repeated electroconvulsive treatment on plasma beta-endorphin, growth hormone, prolactin and cortisol secretion in depressed patients. Psychopharmacology (Berl) 93:122–126

    Article  CAS  Google Scholar 

  • Yang Y, Cao J, Xiong W, Zhang J, Zhou Q, Wei H, Liang C, Deng J, Li T, Yang S, Xu L, Xu L (2003) Both stress experience and age determine the impairment or enhancement effect of stress on spatial memory retrieval. J Endocrinol 178:45–54

    Article  PubMed  CAS  Google Scholar 

  • Yau JL, Noble J, Seckl JR (1999) Continuous blockade of brain mineralocorticoid receptors impairs spatial learning in rats. Neurosci Lett 277:45–48

    Article  PubMed  CAS  Google Scholar 

  • Young AH, Gallagher P, Watson S, Del-Estal D, Owen BM, Nicol Ferrier I (2004) Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology 29:1538–1545

    Article  PubMed  CAS  Google Scholar 

  • Zis AP, Yatham LN, Lam RW, Clark CM, Srisurapanont M, McGarvey K (1996) Effect of stimulus intensity on prolactin and cortisol release induced by unilateral electroconvulsive therapy. Neuropsychopharmacology 15:263–270

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This study was partly supported by an unrestricted research grant from the Council of Scientific and Industrial Research, New Delhi.

Author information

Authors and Affiliations

  1. Department of Pharmacology, St. John’s Medical College, Bangalore, 560 034, India

    Nandakumar Nagaraja, Suresh Sudha & B. V. Venkataraman

  2. Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, 560 029, India

    Chittaranjan Andrade & Nagendra Madan Singh

  3. Central Animal Research Facility, National Institute of Mental Health and Neurosciences, Bangalore, 560 029, India

    J. Suresh Chandra

Authors
  1. Nandakumar Nagaraja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chittaranjan Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suresh Sudha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nagendra Madan Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Suresh Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. V. Venkataraman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chittaranjan Andrade.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagaraja, N., Andrade, C., Sudha, S. et al. Glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia. Psychopharmacology 190, 73–80 (2007). https://doi.org/10.1007/s00213-006-0593-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0593-y

Keywords

Search

Navigation