Skip to main content

Advertisement

Log in

The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers

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

Abstract

Rationale

N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have been reported to induce schizophrenia-like symptoms in humans, including memory impairments. Although the NMDA receptor has been shown to impair memory acquisition by disrupting long-term potentiation (LTP), limited research has been done on studying the effects of NMDA antagonists on the post-LTP cascade of events implicated in consolidation as measured by administering the drug after the initial learning experience.

Objective

The purpose of this experiment was to examine the effect of ketamine on mental status and to identify NMDA antagonist-induced memory deficits by comparing the recall performance of items presented both immediately before and during ketamine infusion.

Methods

Thirteen normal controls received a 60-min infusion of ketamine in a randomized double-blind, cross-over design. Mental status was evaluated with the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale. The first 12-item word list was presented immediately before infusion, and two lists were subsequently presented during the infusion. Verbal memory performance was assessed by measuring the delayed cued recall of each list 30 min after its presentation.

Results

At the beginning, subjects experienced perceptual and reality distortion symptoms, followed later by mild subjective effects. Ketamine significantly reduced the delayed recall of words presented immediately before, but not during, drug infusion. Ketamine-induced decrements in verbal recall correlated significantly with plasma ketamine levels.

Conclusion

This study characterizes the behavioral effects associated with ketamine and suggests that ketamine decreases verbal memory performance by interfering with early consolidation processes.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11:180–187

    Article  PubMed  CAS  Google Scholar 

  • Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH (2000) Attenuation of the neuropsychiatric effects of ketamine with lamotrigine. Arch Gen Psychiatry 57:270–276

    Article  PubMed  CAS  Google Scholar 

  • Cotman CW, Monaghan DT, Ganong AH (1988) Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Annu Rev Neurosci 11:61–80

    Article  PubMed  CAS  Google Scholar 

  • Danysz W, Zajaczkowski W, Parsons CG (1995) Modulation of learning processes by ionotropic glutamate receptor ligands. Behav Pharmacol 6:455–474

    PubMed  CAS  Google Scholar 

  • Ghoneim MN, Hinrichs JV, Mewaldt SP, Peterson RC (1985) Ketamine: behavioral effects of subanesthetic doses. J Clin Psychopharmacol 5(2):70–77

    Article  PubMed  CAS  Google Scholar 

  • Handelmann GE, Contreras PC, O'Donohue TL (1987) Selective memory impairment by phencyclidine in rats. Eur J Pharmacol 140:69–73

    Article  PubMed  CAS  Google Scholar 

  • Harborne GC, Watson FL, Healy DT, Groves L (1996) The effects of subanesthetic doses of ketamine on memory, cognitive performance, and subjective experience in healthy volunteers. J Psychopharmacol 10:134–140

    Article  CAS  Google Scholar 

  • Heale V, Harley C (1990) MK-801 and AP5 impair acquisition, but not retention, of the Morris milk maze. Pharmacol Biochem Behav 36:145–149

    Article  PubMed  CAS  Google Scholar 

  • Hetem LAB, Danion JM, Diemunsch P, Brandt C (2000) Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers. Psychopharmacology 152:283–288

    Article  PubMed  CAS  Google Scholar 

  • Izquierdo I, Quillfeldt JA, Zanatta MS, Quevedo J, Schaeffer E, Schmitz PK, Medina JH (1997) Sequential role of hippocampus and amygdala, entorhinal cortex and parietal cortex in formation and retrieval of memory for inhibitory avoidance in rats. Eur J Neurosci 9:786–793

    Article  PubMed  CAS  Google Scholar 

  • Kesner RP, Dakis M, Bolland BL (1993) Phencyclidine disrupts long- but not short-term memory within a spatial learning task. Psychopharmacology 111:85–90

    Article  PubMed  CAS  Google Scholar 

  • Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Arch Gen Psychiatry 51:199–214

    PubMed  CAS  Google Scholar 

  • Krystal JH, Karper LP, Bennett A, D'Souza DC, Abi-Dargham A, Morrissey K, Abi-Saab D, Bremner JD, Bowers MB, Suckow RF, Stetson P, Heninger GR, Charney DS (1998) Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology 135:213–229

    Article  PubMed  CAS  Google Scholar 

  • Krystal JH, D'Souza DC, Karper LP, Bennett A, Abi-Dargham A, Abi-Saab D, Cassello K, Bowers MB, Vegso S, Heninger GR, Charney DS (1999) Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology 145:193–204

    Article  PubMed  CAS  Google Scholar 

  • Krystal JH, Abi-Saab W, Perry E, D'Souza C, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A (2005) Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology 179:303–309

    Article  PubMed  CAS  Google Scholar 

  • Lahti AC, Weiler MA, Michaelidis T, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25(4):455–467

    Article  PubMed  CAS  Google Scholar 

  • LaPorte DJ, Blaxton TA, Michaelidis T, Robertson DU, Weiler MA, Tamminga CA, Lahti AC (2005) Subtle effects of ketamine on memory when administered following stimulus presentation. Psychopharmacology 139:19–30

    Google Scholar 

  • Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, Brier A (1996) NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14:301–307

    Article  PubMed  CAS  Google Scholar 

  • McGaugh JL (2000) Memory—a century of consolidation. Science 287:248–251

    Article  PubMed  CAS  Google Scholar 

  • Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV (2004a) Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study. Psychopharmacology 172:298–308

    PubMed  CAS  Google Scholar 

  • Morgan CJA, Mofeez A, Brandner B, Bromley L, Curran HV (2004b) Acute effects of ketamine on memory systems and psychotic symptoms in healthy volunteers. Neuropsychopharmacology 29:208–218

    Article  PubMed  CAS  Google Scholar 

  • Newcomer JW, Krystal JH (2001) NMDA receptor regulation of memory and behavior in humans. Hippocampus 11:529–542

    Article  PubMed  CAS  Google Scholar 

  • Newcomer JW, Farber NB, Jestovic-Todorovic V, Selke G, Melson AK, Hershey T, Craft S, Olney JW (1999) Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology 20(2):106–118

    Article  PubMed  CAS  Google Scholar 

  • Overton DA (1978) Major theories of state-dependent learning. In: Ho BT, Richards DW, Chute DL (eds) Drug discrimination and state-dependent learning. Academic Press, New York, pp 284–309

    Google Scholar 

  • Oye I, Paulson O, Maurset A (1992) Effects of ketamine on sensory perception: evidence for a role of N-methyl-d-aspartate receptors. J Pharmacol Exp Ther 260:1209–1213

    PubMed  CAS  Google Scholar 

  • Packard MG, Teather LA (1997) Posttraining injections of MK-801 produce a time-dependent impairment of memory in two water maze tasks. Neurobiol Learn Mem 68:42–50

    Article  PubMed  CAS  Google Scholar 

  • Riedel G, Platt B, Micheau J (2003) Glutamate receptor function in learning and memory. Behav Brain Res 140:1–47

    Article  PubMed  CAS  Google Scholar 

  • Rossato JI, Bonini JS, Coitinho AS, Vianna MRM, Medina JH, Cammarota M, Izquierdo I (2004) Retrograde amnesia induced by drugs acting on different molecular systems. Behav Neurosci 118:563–568

    Article  PubMed  CAS  Google Scholar 

  • Rowland LM, Astur RS, Jung RE, Bustillo JR, Lauriello J, Yeo RA (2005) Selective cognitive impairments associated with NMDA receptor blockade in humans. Neuropsychopharmacology 30:633–639

    Article  PubMed  CAS  Google Scholar 

  • Shapiro ML, Caramanos Z (1990) NMDA antagonist impairs acquisition but not performance of spatial working and reference memory. Psychobiology 18(2):231–243

    CAS  Google Scholar 

  • Walker DL, Gold PE (1991) Effects of the novel NMDA antagonist NPC 12626, on long-term potentiation, learning and memory. Brain Res 549:213–221

    Article  PubMed  CAS  Google Scholar 

  • Winters BD, Bussey TJ (2005) Glutamate receptors in perirhinal corex mediate encoding, retrieval, and consolidation of object recognition memory. J Neurosci 25(17):4243–4251

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adrienne C. Lahti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parwani, A., Weiler, M.A., Blaxton, T.A. et al. The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers. Psychopharmacology 183, 265–274 (2005). https://doi.org/10.1007/s00213-005-0177-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0177-2

Keywords

Navigation