Skip to main content
Log in

Zolpidem and triazolam do not affect the nocturnal sleep-induced memory improvement

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

Abstract

Rationale

It is widely accepted that sleep facilitates memory consolidation. Hypnotics (e.g., benzodiazepines), which reportedly increase sleep efficiency but also modify sleep architecture, could affect memory improvement that occurs during sleep.

Objectives

The present study examined the effects of single doses of two short half-life hypnotics, zolpidem and triazolam, on sleep-induced improvement of memory.

Methods

Twenty-two healthy volunteers participated in this randomized, double-blind, crossover study. All subjects received a single oral dose of zolpidem (10 mg), triazolam (0.25 mg) or placebo at 9 p.m. and slept for 7.5±0.2 h. The effect of sleep on memory was investigated by comparing the performance of this group of volunteers with a group of 21 subjects in wakefulness condition. Declarative memory was evaluated by using a free-recall test of ten standard word and seven nonword lists. Subjects memorized the word and nonword lists 1 h before dosing and they were asked to recall the memorized lists 10 h after dosing. Digit symbol substitution test (DSST) and forward and backward digit tests were also given 1 h before and 10 h after dosing.

Results

Subjects who slept remembered more nonwords than those in wakefulness condition, but they did not recall significantly more standard words. Neither zolpidem nor triazolam affected the enhanced nonword recall observed after sleep. Finally, none of the hypnotics affected the improvement in the DSST performance of subjects who slept.

Conclusions

The hypnotics tested did not interfere with the nocturnal sleep-induced improvement of memory.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aeschbach D, Dijk DJ, Trachsel L, Brunner DP, Borbely AA (1994) Dynamics of slow-wave activity and spindle frequency activity in the human sleep EEG: effect of midazolam and zopiclone. Neuropsychopharmacology 11:237–244

    PubMed  CAS  Google Scholar 

  • Berlin I, Warot D, Hergueta T, Molinier P, Bagot C, Puech AJ (1993) Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects. J Clin Psychopharmacol 13:100–106

    Article  PubMed  CAS  Google Scholar 

  • Byrnes JJ, Greenblatt DJ, Miller LG (1992) Benzodiazepine receptor binding of nonbenzodiazepines in vivo: alpidem, zolpidem and zopiclone. Brain Res Bull 29:905–908

    Article  PubMed  CAS  Google Scholar 

  • Cajochen C, Knoblauch V, Wirz-Justice A, Krauchi K, Graw P, Wallach D (2004) Circadian modulation of sequence learning under high and low sleep pressure conditions. Behav Brain Res 151:167–176

    Article  PubMed  Google Scholar 

  • Coenen AM, van Luijtelaar EL (1997) Effects of benzodiazepines, sleep and sleep deprivation on vigilance and memory. Acta Neurol Belg 97:123–129

    PubMed  CAS  Google Scholar 

  • Condemarin M, Blonquist M (1970) La dislexia. Manual de lectura correctativa, 1st edn. Editorial Universitaria, Santiago de Chile

    Google Scholar 

  • Dean A, Voss D (1999) Design and analysis of experiments. Springer, Berlin Heidelberg New York

    Book  Google Scholar 

  • Drover D, Lemmens H, Naidu S, Cevallos W, Darwish M, Stanski D (2000) Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zolpidem. Clin Ther 22:1443–1461

    Article  PubMed  CAS  Google Scholar 

  • Drummond SP, Brown GG, Gillin JC, Stricker JL, Wong EC, Buxton RB (2000) Altered brain response to verbal learning following sleep deprivation. Nature 403:655–657

    Article  PubMed  CAS  Google Scholar 

  • Dupont WD (2002) Statistical modeling for biomedical researchers: a simple introduction to the analysis of complex data. Cambridge University Press, Cambridge

    Google Scholar 

  • Feinberg I, Maloney T, Campbell IG (2000) Effects of hypnotics on the sleep EEG of healthy young adults: new data and psychopharmacologic implications. J Psychiatr Res 34:423–438

    Article  PubMed  CAS  Google Scholar 

  • Ficca G, Salzarulo P (2004) What in sleep is for memory. Sleep Med 5:225–230

    Article  PubMed  Google Scholar 

  • Ficca G, Lombardo P, Rossi L, Salzarulo P (2000) Morning recall of verbal material depends on prior sleep organization. Behav Brain Res 112:159–163

    Article  PubMed  CAS  Google Scholar 

  • Friedman H, Greenblatt DJ, Burstein ES, Harmatz JS, Shader RI (1986) Population study of triazolam pharmacokinetics. Br J Clin Pharmacol 22:639–642

    PubMed  CAS  Google Scholar 

  • Friedman H, Greenblat DJ, Peters GR, Metzler CM, Charlton MD, Harmatz JS, Antal EJ, Sanborn EC, Francom SF (1992) Pharmacokinetics and pharmacodynamics of oral diazepam: effect of dose, plasma concentration, and time. Clin Pharmacol Ther 52:139–150

    Article  PubMed  CAS  Google Scholar 

  • Gais S, Plihal W, Wagner U, Born J (2000) Early sleep triggers memory for early visual discrimination skills. Nat Neurosci 3:1335–1339

    Article  PubMed  CAS  Google Scholar 

  • Ghoneim MM, Mewaldt SP (1990) Benzodiazepine and human memory: a review. Anesthesiology 72:926–938

    Article  PubMed  CAS  Google Scholar 

  • Giuditta A, Ambrosini MV, Montagnese P, Mandile P, Cotugno M, Grassi Zucconi G, Vescia S (1995) The sequential hypothesis of the function of sleep. Behav Brain Res 69:157–166

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI (1988) Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 44:326–334

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Harmatz JS, von Moltke LL, Ehrenberg BL, Harrel L, Corbett K, Counihan M, Graf JA, Darwish M, Mertzanis P, Martin PT, Cevallos WH, Shader RI (1998) Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo. Clin Pharmacol Ther 64:553–561

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Harmatz JS, von Moltke LL, Wright CE, Durol AL, Harrel-Joseph LM, Shader RI (2000) Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences. J Pharmacol Exp Ther 293:435–443

    PubMed  CAS  Google Scholar 

  • Harrison Y, Horne JA (1997) Sleep deprivation affects speech. Sleep 20:871–877

    PubMed  CAS  Google Scholar 

  • Harrison Y, Horne JA (1998) Sleep loss impairs short and novel language tasks having a prefrontal focus. J Sleep Res 7:95–100

    Article  PubMed  CAS  Google Scholar 

  • Hulme C, Maughan S, Brown GDA (1991) Memory for familiar and unfamiliar words: evidence for a long-term memory contribution to short-term memory span. J Mem Lang 30:685–701

    Article  Google Scholar 

  • Hulme C, Roodenrys S, Brown GDA, Mercer R (1995) The role of long-term memory mechanism I memory span. Br J Psychol 86:527–536

    Google Scholar 

  • Itier V, Depoortere H, Scatton B, Avenet P (1996) Zolpidem functionally discriminates subtypes of native GABAA receptors in acutely dissociated rat striatal and cerebellar neurons. Neuropharmacology 35:137–145

    Article  PubMed  CAS  Google Scholar 

  • Jenkins JK, Dallenbach KM (1924) Obliviscence during sleep and waking. Am J Psychol 35:605–612

    Article  Google Scholar 

  • Kanno O, Watanabe H, Kazamatsuri H (1993) Effects of zopiclone, flunitrazepam, triazolam and levomepromazine on the transient change in sleep–awake schedule: polygraphic study, and the evaluation of sleep and daytime condition. Prog Neuro-Psychopharmacol Biol Psychiatry 17:229–239

    Article  CAS  Google Scholar 

  • Kanno O, Sasaki T, Watanabe H, Takazawa S, Nakagome K, Nakajima T, Ichikawa I, Akaho R, Suzuki M (2000) Comparison of the effects of zolpidem and triazolam on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy young volunteers. Prog Neuro-Psychopharmacol Biol Psychiatry 24:897–910

    Article  CAS  Google Scholar 

  • Karni A, Tanne D, Rubenstein BS, Askenasy JJ, Sagi D (1994) Dependence on REM sleep of overnight improvement of a perceptual skill. Science 265:679–682

    Article  PubMed  CAS  Google Scholar 

  • Koulack D (1997) Recognition memory, circadian rhythms, and sleep. Percept Mot Skills 85:99–104

    PubMed  CAS  Google Scholar 

  • Lancel M (1999) Role of GABA receptors in the regulation of sleep: initial sleep responses to peripherally administered modultaros and agonists. Sleep 22:33–42

    PubMed  CAS  Google Scholar 

  • Lee AK, Wilson MA (2002) Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36:1183–1194

    Article  PubMed  CAS  Google Scholar 

  • Lobo BL, Greene WL (1997) Zolpidem: distinct from triazolam? Ann Pharmacother 31:625–632

    PubMed  CAS  Google Scholar 

  • Maquet P (2001) The role of sleep in learning and memory. Science 294:1048–1052

    Article  PubMed  CAS  Google Scholar 

  • Maquet P, Laureys S, Peigneux P, Fuchs S, Petiau C, Phillips C, Aerts J, Del Fiore G, Degueldre C, Meulemans T, Luxen A, Franck G, Van Der Linden M, Smith C, Cleeremans A (2000) Experience-dependent changes in cerebral activation during human REM sleep. Nat Neurosci 3:831–836

    Article  PubMed  CAS  Google Scholar 

  • Maquet P, Schwartz S, Passingham R, Frith C (2003) Sleep-related consolidation of a visuomotor skill: brain mechanisms as assessed by functional magnetic resonance imaging. J Neurosci 23:1432–1440

    PubMed  CAS  Google Scholar 

  • Mazzoni G, Gori S, Formicola G, Gneri C, Massetani R, Murri L, Salzarulo P (1999) Word recall correlates with sleep cycles in elderly subjects. J Sleep Res 8:185–188

    Article  PubMed  CAS  Google Scholar 

  • Mednick S, Nakayama K, Stickgold R (2003) Sleep-dependent learning: a nap is as good as a night. Nat Neurosci 6:697–698

    Article  PubMed  CAS  Google Scholar 

  • Nakajima T, Sasaki T, Nakagome K, Takazawa S, Ikebuchi E, Ito Y, Miyazawa Y, Tanaka M, Kanno O (2000) Comparison of the effects of zolpidem and zopiclone on nocturnal sleep and sleep latency in the morning: a cross-over study in healthy young volunteers. Life Sci 67:81–90

    Article  PubMed  CAS  Google Scholar 

  • Nesca M, Koulack D (1994) Recognition memory, sleep and circadian rhythms. Can J Exp Psychol 48:359–379

    Article  PubMed  CAS  Google Scholar 

  • Nowell PD, Mazumdar S, Buysse DJ, Dew MA, Reynolds CF III, Kupfer DJ (1997) Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy. J Am Med Assoc 278:2170–2177

    Article  CAS  Google Scholar 

  • Osterrieth PA (1944) Le test de copy d’une figure complete. Arch Psychol 30:206–356

    Google Scholar 

  • Plihal W, Born J (1999) Effects of early and late nocturnal sleep on priming and spatial memory. Psyhophysiology 36:571–582

    Article  CAS  Google Scholar 

  • Plihal W, Pietrowsky R, Born J (1999) Dexamethasone blocks sleep induced improvement of declarative memory. Psychoneuroendocrinology 24:313–331

    Article  PubMed  CAS  Google Scholar 

  • Risetti FJ, Himmel E, Maltes S, González JA, Olmos S (1989) Estandarización del Inventario Multifásico de la Personalidad Minnesota (MMPI) en Población Adulta Chilena. Rev Chil Psicol 10:41–62

    Google Scholar 

  • Roth T, Roehrs TA (1992) Issues in the use of benzodiazepine therapy. J Clin Psychiatry 53:14–18

    PubMed  Google Scholar 

  • Roth T, Costa e Silva JA, Chase MH (2001) Sleep and cognitive (memory) function: research and clinical perspectives. Sleep Med 2:379–387

    Article  PubMed  CAS  Google Scholar 

  • Saint-Aubin J, Poirier M (2000) Immediate serial recall of words and nonwords: tests of the retrieval-based hypothesis. Psychon Bull Rev 7:332–340

    PubMed  CAS  Google Scholar 

  • Sanna E, Busonero F, Talani G, Carta M, Massa F, Peis M, Maciocco E, Biggio G (2002) Comparison of the effects of zaleplon, zolpidem, and triazolam at various GABA(A) receptor subtypes. Eur J Pharmacol 451:103–110

    Article  PubMed  CAS  Google Scholar 

  • Silva A, Collao A, Orellana M, Meléndez J, Caviedes P, Cárdenas AM (2003) Zopiclone, but not brotizolam, impairs memory storage during sleep. Neurosci Res 47:241–243

    Article  PubMed  CAS  Google Scholar 

  • Skaggs WE, McNaughton BL (1996) Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science 271:1870–1873

    Article  PubMed  CAS  Google Scholar 

  • Smith C (1996) Sleep states, memory processes and synaptic plasticity. Behav Brain Res 78:49–56

    Article  PubMed  CAS  Google Scholar 

  • Smith C, Rose GM (1997) Posttraining paradoxical sleep in rats is increased after spatial learning in the Morris water maze. Behav Neurosci 111:1197–1204

    Article  PubMed  CAS  Google Scholar 

  • StataCorp (2003) Stata statistical software: release 8.0. Stata Corporation, College Station, TX

    Google Scholar 

  • Stickgold R (1998) Sleep: off-line memory reprocessing. Trends Cogn Sci 2:484–492

    Article  Google Scholar 

  • Stickgold R, Scott L, Rittenhouse C, Hobson JA (1999) Sleep-induced changes in associative memory. J Cogn Neurosci 11:182–193

    Article  PubMed  CAS  Google Scholar 

  • Stickgold R, James L, Hobson JA (2000a) Visual discrimination learning requires sleep after training. Nat Neurosci 3:1237–1238

    Article  PubMed  CAS  Google Scholar 

  • Stickgold R, Whidbee D, Schirmer B, Patel V, Hobson JA (2000b) Visual discrimination task improvement: a multi-step process occurring during sleep. J Cogn Neurosci 12:246–254

    Article  PubMed  CAS  Google Scholar 

  • Tan X, Uchida S, Matsuura M, Nishihara K, Kojima T (2003) Long-, intermediate- and short-acting benzodiazepine effects on human sleep EEG spectra. Psychiatry Clin Neurosci 57:97–104

    Article  PubMed  CAS  Google Scholar 

  • Twisk JWR (2003) Applied longitudinal data analysis for epidemiology: a practical guide. Cambridge University Press, Cambridge

    Google Scholar 

  • Verbeke G, Molenberghs G (1997) Linear mixed models in practice: a SAS-oriented approach. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Verbeke G, Molenberghs G (2000) Linear mixed models for longitudinal data. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Warot D, Bensimon G, Danjou P, Puech J (1987) Comparative effects of zopiclone, triazolam and placebo on memory and psychomotor performance in healthy volunteers. Fundam Clin Pharmacol 1:145–152

    Article  PubMed  CAS  Google Scholar 

  • Wechsler D (1988) WAIS: test de inteligencia para adultos, 1st edn. Piados, Buenos Aires

    Google Scholar 

  • Wilson MA, McNaughton BL (1994) Reactivation of hippocampal ensemble memories during sleep. Science 265:676–679

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Professor Alberto Caro (Departamento de Estadística de la Facultad de Ciencias, Universidad de Valparaíso), Sergio Jiménez and Javier Díaz (medical students, Escuela de Medicina, Universidad de Valparaíso), and David Memmott for their invaluable help. This project was supported by DIPUV 07/2002 (Universidad de Valparaíso.)

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ana M. Cárdenas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meléndez, J., Galli, I., Boric, K. et al. Zolpidem and triazolam do not affect the nocturnal sleep-induced memory improvement. Psychopharmacology 181, 21–26 (2005). https://doi.org/10.1007/s00213-005-2228-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-2228-0

Keywords

Navigation