, Volume 108, Issue 3, pp 345–351 | Cite as

Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers

  • Jean-Marie Danion
  • Siegfried Peretti
  • Danielle Grangé
  • Miloslav Bilik
  • Jean-Louis Imbs
  • Léonard Singer
Original Investigations


To assess the influence of neuroleptics on explicit memory and two forms of implicit memory, repetition priming and cognitive skill learning, the effects of two low doses of chlorpromazine (12.5 and 25 mg orally) were contrasted to those of lorazepam (2.5 mg orally) and of a placebo using a free-recall task, a word-completion task and repeated testing on the Tower of Toronto puzzle, a version of the Tower of Hanoi puzzle. Seventy-two healthy volunteers took part in this double-blind study. Chlorpromazine spared free-recall and word-completion performance, but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently. Lorazepam induced an opposite pattern of memory disruption. These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine. They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems, the latter, but not the former, being dependent upon dopaminergic systems.

Key words

Chlorpromazine Dopamine Human Learning Lorazepam Memory 


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  1. Baldessarini RJ (1980) Drugs and the treatment of psychiatric disorders. In: Goodman, Gilman's (eds) The pharmacological basis of therapeutics, ch. 19. Macmillan, New York, pp 391–418Google Scholar
  2. Brown MW, Brown J, Bowes JB (1989) Absence of priming coupled with substantially preserved recognition in lorazepam induced amnesia. Q J Exp Psychol 41A [3]:599–617Google Scholar
  3. Brozowski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205:929–932Google Scholar
  4. Cohen NJ, Squire LR (1980) Preserved learning and retention of pattern-analysing skill in amnesia: dissociation of knowing how and knowing that. Science 210:207–210Google Scholar
  5. Cohen NJ, Eichenbaum H, Deacedo BS, Corkin S (1985) Different memory systems underlying acquisition of procedural and declarative knowledge. Ann NY Acad Sci 444:54–71Google Scholar
  6. Danion JM, Zimmermann MA, Willard-Schroeder D, Grangé D, Singer L (1989) Diazepam induces a dissociation between explicit and implicit memory. Psychopharmacology 99:238–243Google Scholar
  7. Danion JM, Zimmermann MA, Willard-Schroeder D, Grangé D, Welsch M, Imbs JL, Singer L (1990) Effects of scopolamine, trimipramine and diazepam on explicit memory and repetition priming in healthy volunteers. Psychopharmacology 102:422–424Google Scholar
  8. Danion JM, Willard-Schroeder D, Zimmermann MA, Grangé D, Schlienger JL, Singer L (1991) Explicit memory and repetition priming in depression. Arch Gen Psychiatry 48:707–711Google Scholar
  9. Fang JC, Hinrichs JV, Ghoneim MM (1987) Diazepam and memory: evidence for spared memory function. Pharmacol Biochem Behav 28:347–352Google Scholar
  10. Goldberg TE, Saint-Cyr JA, Weinberger DR (1990) Assessment of procedural learning and problem solving in schizophrenic patients by Tower of Hanoi type tasks. J Neuropsy Clin Neurosci 2:165–173Google Scholar
  11. Graf P, Mandler G, Haden PE (1982) Simulating amnesic symptoms in normal subjects. Science 218:1243–1244Google Scholar
  12. Graf P, Squire LR, Mandler G (1984) The information that amnesic patients do not forget. J Exp Psychol [Learn Mem Cogn] 10:164–178Google Scholar
  13. Hastroudi S, Parker ES, Delisi LE, Wyatt RJ, Mutter SA (1984) Intact retention in acute alcohol amnesia. J Exp Psychol [Learn Mem Cogn] 10:156–163Google Scholar
  14. Heindel WC, Butters N, Salmon DP (1988) Impaired learning of a motor skill in patients with Huntington's disease. Behav Neurosci 102:141–147Google Scholar
  15. Heindel WC, Salmon DP, Shultz CW, Walicke PA, Butters NJ (1989) Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients. Neuroscience 9:582–587Google Scholar
  16. King DJ (1990) The effect of neuroleptics on cognitive and psychomotor function. Br J Psychiatry 157:799–811Google Scholar
  17. Kornetsky C, Humphries O (1957) Relationship between effects of a number of centrally acting drugs and personality. AMA Arch Neurol Psy 77:325–327Google Scholar
  18. Kornetsky C, Pettit M, Wynne R (1959) A comparison of the psychological effects of acute and chronic administration of chlorpromazine and secobarbital (quinalbarbitone) in schizophrenic patients. J Ment Sci 105:190–198Google Scholar
  19. Kyriakopoulos AA, Greenblatt DJ, Shader RI (1978) Clinical pharmacokinetics of lorazepam: a review. J Clin Psychiatry 39:16–23Google Scholar
  20. Lebart L, Morineau A, Warwick KM (1984) Multivariate descriptive statistical analysis. Wiley, New York, pp 109–145Google Scholar
  21. Lister RG, File SE (1984) The nature of lorazepam-induced amnesia. Psychopharmacology 83:183–187Google Scholar
  22. Martone M, Butters N, Payne M, Becker JT, Sax DS (1984) Dissociations between skill learning and verbal recognition in amnesia and dementia. Arch Neurol 41:965–970Google Scholar
  23. Midha KK, Hawes EM, Hubbard JW, Korchinski ED, Mc Kay G (1989) Intersubject variation in the pharmacokinetics of chlorpromazine in healthy men. J Clin Psychopharmacol 1:4–8Google Scholar
  24. Mishkin M, Malamut B, Bachevalier J (1984) Memories and habits: two neural systems. In: Lynch G, Mc Gaugh JL, Weinberger NM (eds) Neurobiology of learning and memory. Guilford, New York, pp 65–77Google Scholar
  25. Richardson-Klavehn A, Bjork RA (1988) Measures of memory. Annu Rev Psychol 39:475–543Google Scholar
  26. Rinne JO, Lônnberg P, Marjamäki P (1990) Age-dependent decline in human brain dopamine D1 and D2 receptors. Brain Res 508:349–352Google Scholar
  27. Saint-Cyr JA, Taylor AE, Lang AE (1988) Procedural learning and neostriatal dysfunction in man. Brain 111:941–959Google Scholar
  28. Schacter DL (1987) Implicit memory: history and current status. J Exp Psychol [Learn Mem Cogn] 13:501–518Google Scholar
  29. Sellal F, Danion JM, Kauffmann-Müller F, Granǵe D, Imbs JL, Van der Linden M, Singer L (1992) Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers. Psychopharmacology 108:371–379Google Scholar
  30. Shallice T (1982) Specific impairments of planning. Philos Trans R Soc London Ser B 298:199–209Google Scholar
  31. Shimamura AP, Salmon DP, Squire LR, Butters N (1987) Memory dysfunction and word priming in dementia and amnesia. Behav Neurosci 101:347–351Google Scholar
  32. Simon H, Scatton B, Le Moal M (1980) Dopaminergic A10 neurones are involved in cognitive function. Nature 286:150–151Google Scholar
  33. Squire LR (1986) Mechanisms of memory. Science 232:1612–1619Google Scholar
  34. Squire LR, Cohen NJ (1984) Human memory and amnesia. In: Lynch G, Mc Gaugh JL, Weinberger NM (eds) Neurobiology of learning and memory. Guilford, New York, pp 3–63Google Scholar
  35. Tulving E, Schacter DL (1990) Priming and human memory systems. Science 247:301–306Google Scholar
  36. Warrington EK, Weiskrantz L (1970) Amnesic syndrome: consolidation or retrieval? Nature 228:628–630Google Scholar
  37. Wechsler D (1955) Manual for the Wechsler adult intelligence scale. Psychological Corporation, New YorkGoogle Scholar
  38. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Jean-Marie Danion
    • 1
  • Siegfried Peretti
    • 1
  • Danielle Grangé
    • 2
  • Miloslav Bilik
    • 1
  • Jean-Louis Imbs
    • 3
  • Léonard Singer
    • 1
  1. 1.Department of PsychiatryHôpitaux UniversitairesStrasbourg CedexFrance
  2. 2.Unite de StatistiquesCentre de Calcul du CNRSStrasbourgFrance
  3. 3.Institut de PharmacologieUnité de Pharmacologie Clinique, Faculté de MédecineStrasbourgFrance

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