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The effects of a benzodiazepine receptor antagonist β-carboline ZK-93426 on scopolamine-induced impairment on attention, memory and psychomotor skills

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Abstract

The effects of a single dose of scopolamine alone and in combination with ZK 93426 (a β-carboline antagonist at the GABAA/BZ receptor complex with weak inverse agonist activity) were tested in two studies. In one study (study 1) the emphasis of enquiry was on different stages of information processing measured by a psychometric battery; in the second study (study 2) performance at different stages of memory and psychomotor abilities was tested and electroencephalogram recordings and video-tracking were also performed. Each study consisted of two parts, part I in which scopolamine (0.5 mg; 1 ml) or placebo were administered subcutaneously, and part II in which scopolamine (0.5 mg; 1 ml) was administered subcutaneously followed by an intravenous injection of ZK 93426 (0.04 mg; 0.04 ml/kg) or placebo. Thirty-six volunteers, who were randomly allocated to receive one of the two treatments (n=18 per treatment), participated in each part. In study 1 attention was measured by a continuous attention task and a rapid information processing task, vigilance was measured by a visual vigilance task, and working memory and reasoning were evaluated by a logical reasoning task. A visual memory task was also included to measure acquisition and retention. In study 2 acquisition and short term storage and retrieval were measured by a word lists-Buschke restricted reminding procedure, and retention was tested by delayed recall and recognition. Psychomotor performance was assessed by measuring tapping speed (related to gross motoric abilities) and a pegboard task (related to fine motoric abilities). A task to measure working memory, the Pauli test, was also included. In study 1 scopolamine significantly impaired performance in the attentional and vigilance tasks (P<0.05), but there was no effect in the logical reasoning task main measurements of time and accuracy. In study 2, scopolamine also impaired performance in the psychomotor tasks (P<0.05) and the Pauli test. ZK 93426 partially antagonised most of the effects of scopolamine on memory and attention, suggesting that an interaction between the GABA-ergic and cholinergic systems is reflected in measurements of both attention and memory. In general a dissociation was found in the effects of scopolamine on memory, i.e. scopolamine impaired performance during all acquisition measurements but left retention unaffected.

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References

  • Aarsland D, Larsen JP, Reinvang I, Aasland AM (1994) Effects of cholinergic blockade on language in healthy young women implications for the cholinergic hypothesis in dementia of the Alzheimer type. Brain 117:377–1384

    Google Scholar 

  • Arnold W (1970) Der Pauli Test. Anweisung Zur Sachgemäße Durchführung, Auswertung Und Anwendung Des Kraepelinschen Arbeitsversuches. J A Bath Verlag, München

    Google Scholar 

  • Baddeley (1968) A 3 min reasoning test based on grammatical transformation. Psychon Sci 10:341–342

    Google Scholar 

  • Beatty WW, Butters N, Janosky DS (1986) Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia. Behav Neural Biol 45:196–211

    Google Scholar 

  • Blin J, Piercey MF, Giuffra ME, Mouradian MM, Chase TN (1994) Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography. J Neurol Sci 123:44–51

    Google Scholar 

  • Bowen DM, Francis PT, Chessel IP, Webster Mt (1994) Neurotransmission — the link integrating Alzheimer research? Trends Neurosci 17:149–150

    Google Scholar 

  • Brass EP, Polinsky R, Sramek JJ, Moore M, Jones D, Veroff AE, Wardle TS, Cutler NR (1995) Effects of the cholinomimetic Sdz Ens-163 on scopolamine-induced cognitive impairment in humans. J Clin Psychopharmacol 15:58–62

    Google Scholar 

  • Brioni JD (1993) Role of GABA during the multiple consolidation of memory. Drug Dev Res 28:3–27

    Google Scholar 

  • Brown MW, Brown J, Bowes JB (1989) Absence of priming coupled with substantially preserved recognition in lorazepam-induced amnesia. Q J Exp Psychol 41a:599–617

    Google Scholar 

  • Buschke H, Altman Fuld P (1974) Evaluating storage, retention and retrieval in disordered memory and learning. Neurology 24:1019–1025

    Google Scholar 

  • Caine ED, Weingartner H, Ludlow CL, Cudahy EA, Wehry S (1981) Qualitative analysis of scopolamine induced amnesia. Psychopharmacology 74:74–80

    Google Scholar 

  • Callaway E (1984) Human information processing: some effects of methylphenate, age and scopolamine. Biol Psychiatry 19:649–666

    Google Scholar 

  • Cole BJ, Jones GH (1995) Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive-avoidance. Psychopharmacology 118:37–41

    Google Scholar 

  • Curran HV, Schifano F, Lader M (1991) Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on Memory, psychomotor performance and mood. Psychopharmacology 100:463–471

    Google Scholar 

  • Deutsch JA (1971) The cholinergic synapse and the site of memory. Science 174:788–794

    Google Scholar 

  • Dorow R, Horowski R, Paschelke G, Amin M, Braestrup C (1983) Severe anxiety induced by Fg 7142, aβ-carboline ligand for benzodiazepine receptors. Lancet 2:98

    Google Scholar 

  • Dorow R, Berenberg D, Duka T, Sauerbrey N (1987) Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788. Psychopharmacology 93:507–514

    Google Scholar 

  • Drachman DA, Leavitt J (1974) Human memory and the cholinergic system. Arch Neurol 30:113–121

    Google Scholar 

  • Drachman DA, Sahakian BJ (1979) Effects of cholinergic agents on human learning and memory. In: Barbeau A, Crowdon JH, Wurtman RJ (eds) New York, Nutrition and the brain. Raven Press, pp 351–366

    Google Scholar 

  • Duka T (1991) Bidirectional activity of benzodiazepine receptor ligands in cognitive functions in humans. in: Briley M, File SE (eds) New concepts in anxiety. Macmillan London, pp 440–458

    Google Scholar 

  • Duka T, Dorow R (1995) Human experimental psychopharmacology of benzodiazepine receptor inverse agonists and antagonists. In Sarter M, Nutt DJ (eds) Inverse agonists at benzodiazepine receptors. Wiley, New York, pp 243–270

    Google Scholar 

  • Duka T, Stephens DN, Krause W, Dorow R (1987) Humans studies on the benzodiazepine receptor antagonistβ-carboline Zk 93 426:preliminary observations on psychotropic activity. Psychopharmacology 93:421–427

    Google Scholar 

  • Duka T, Edelmann V, Schütt B, Dorow R (1988a)β-Carbolines as tools in memory research. Human data with theβ-carboline ZK 93 426. In: Hindmarch I, Ott H, Roth T (eds) Benzodiazepine receptor ligands, memory and information processing. Psychopharmacology Suppl. 6. Springer, New York, pp 246–261

    Google Scholar 

  • Duka T, Goerke D., Dorow R, Höller L, Fichte K (1988b) Human studies on the benzodiazepine receptor antagonistβ-carboline Zk 93 426: antagonism of lormetazepam's psychotropic effects. Psychopharmacology 95:463–472

    Google Scholar 

  • Duka T, Stephens DN, Dorow R (1990) Cognitive enhancing properties of antagonistβ-carbolines: new insights into clinical research on the treatment of dementias? In: Maurer K, Riederer P, Beckmann H (eds) Alzheimer's disease epidemiology, neuropathology, neurochemistry clinics. Springer, Wien, pp 55–564

    Google Scholar 

  • Duka T, Edelmann V, Dorow R, Fichte K (1992) Scopolamine induced amnesia in humans: lack of effects of the benzodiazepine receptor antagonistβ-carboline Zk 93 426. J Psychopharmacol 6:382–388

    Google Scholar 

  • Duka T, Redemann B, Voet B (1995) Scopolamine and lorazepam exert different patterns of effects in a test battery assessing stages of information processing. Psychopharmacology 119:315–324

    Google Scholar 

  • Frith CD, Richardson JTE, Samuel M, Crow TJ, Mc Kenna PJ (1984) The effects of intravenous diazepam and hyoscine upon human memory. Q J Exp Psychol 36a:133–144

    Google Scholar 

  • Ghoneim MM, Mewald SP (1975) Effects of diazepam and scopolamine on storage, retrieval and organizational processes in memory. Psychopharmacologica 44:257–262

    Google Scholar 

  • Ghoneim MM, Mewald SP (1977) Studies on human memory: the interactions of diazepam, scopolamine and physostigmine. Psychopharmacology 52:1–6

    Google Scholar 

  • Imperato A, Dazzi L, Obinu MC, Gessa GL, Biggio G (1993) Inhibition of hippocampal acetylcholine-rel by benzodiazepines — antagonism by fllumazenil. Eur J Pharmacol 238:135–137

    Google Scholar 

  • Kopelman MD (1987) How far could cholinergic depletion account for the memory deficits of Alzheimer-type dementia or the alcoholic Korsakoff syndrome? In: Stahl SM, Iversen SD, Goodman EC (eds) Cognitive neurochemistry Eds Oxford University Press, Oxford, pp 303–327

    Google Scholar 

  • Lines CR, Ambrose JH, Heald A, Traub M (1993) A double-blind, placebo-controlled study of the effects of eptastigmine on scopolamine-induced cognitive deficits in healthy male-subjects. Human psychopharmacol Clin Exp 8:271–278

    Google Scholar 

  • Litvan I, Sirigu A, Toothman J, Grafman A (1995) What can preservation of autobiographical memory after muscarinic blockade tell us about the scopolamine model of dementia. Neurology 45:387–389

    Google Scholar 

  • Mauri M, Sinforiani E, Reverberi F, Merlo P, Bono G (1994) Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers. Arch Gerontol Geriatr 18:133–139

    Google Scholar 

  • Molchan SE, Matochik JA, Zametkin AJ, Szymanski HV, Cantillon M, Cohen RM, Sunderland T (1994) A double FDG Pet study of the effects of scopolamine in older adults. Neuropsycho-pharmacology. 10[3]:191–198

    Google Scholar 

  • Ott H, Mcdonald RJ, Fichte K, Hermann WM (1982) Interpretation of correlation between EEG power spectra and psychological performance variables within the concepts of “subvigilance”, “attention” and “psychomotoric impulsion”. In: Hermann VM (ed) EEG In Drug Research. Gustav Fischer, Stuttgart New York, pp 227–247

    Google Scholar 

  • Ott H, Rohloff A, Aufdembrinke B, Fichte K (1988) Anterograde and retrograde amnesia after lormetazepam and flunitrazepam. In: Hindmarch I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Psychopharmacology Series 6, Springer, New York, pp 180–194

    Google Scholar 

  • Preda L, Alberoni M, Bressi S, Cattaneo C, Parini J, Canal N, Franceschi M (1993) Effects of acute doses of oxiracetam in the scopolamine model of human amnesia. Psychopharmacology 110:421–426

    Google Scholar 

  • Randt CT, Brown ER, Osborne DP (1980) A memory test for longitudinal measurement of mild to moderate deficits. Clin Neuropsychol II 4:20–32

    Google Scholar 

  • Richardson JTE, Frith CD, Scott E, Crow T, Cunningham-Owens D (1984) The effects of intravenous diazepam and hyoscine upon recognition memory. Behav Brain Res 14:193–199

    Google Scholar 

  • Rusted JM (1994) Cholinergic blockade and human information processing: are we asking the right questions? J Psychopharmacol 8:54–59

    Google Scholar 

  • Rusted JM, Warburton DM (1988) The effects of scopolamine on working memory in healthy young volunteers Psychopharmacology 96:145–152

    Google Scholar 

  • Rusted JM, Warburton DM (1989) Effects of scopolamine on verbal memory; a retrieval or acquisition deficit? Neuropsychobiology 21:76–83

    Google Scholar 

  • Rusted JM, Eaton-Williams P, Warburton DM (1991) A comparison of the effects of scopolamine and diazepam on working memory Psychopharmacology 105:442–445

    Google Scholar 

  • Sahakian BJ (1988) Cholinergic drugs and human cognitive performance. In: Iversen Ll, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology Vol. 20. Plenum Press, London, pp 393–424

    Google Scholar 

  • Sahakian BJ, Coull JT (1994) Nicotine and tetrahydroaminoacradine — evidence for improved attention in patients with dementia of the Alzheimer type. Drug Dev Res 31:80–88

    Google Scholar 

  • Safer DJ, Allen RP (1971) The central effects of scopolamine in man. Biol Psychiatry 3:347–355

    Google Scholar 

  • Sarter M, Schneider HH, Stephens DN (1988) Treatment strategies for senile dementia: antagonistβ-carbolines. Trends Neurosci 11:13–17

    Google Scholar 

  • Siegfried K (1995) The efficacy of cholinergic drugs in patients with Alzheimer's disease. Focus on the aminoacridines. Hum psychopharmacol clin Exp 10:89–96

    Google Scholar 

  • Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA, Murphy DI (1987) Anticholinergic sensitivity in patients with dementia of the Azheimer type and age matched controls: a dose response study. Arch Gen Psychiatry 44:418–426

    Google Scholar 

  • Tiplady B (1985) An automated test battery for the detection of changes in mental function and psychomotor performance. Br J Clin Pharmacol 20:305p

  • Tiplady B (1992) Continuous attention: rationale and discriminant validation of a test designed for use in psychopharmacology. Behav Res Methods Instr Comput 24:16–21

    Google Scholar 

  • Warburton DM, Rusted JM (1993) Cholinergic control of cognitive resources. Neuropsychobiology 28:43–46

    Google Scholar 

  • Weingartner HJ (1985) Models of memory dysfunctions. Ann NY Acad Sci 444:359–369

    Google Scholar 

  • Weingartner HJ, Hommer D, Lister RG, Thompson K, Wolkowitz O (1992) Selective effects of triazolam on memory. Psychopharmacology 106:341–345

    Google Scholar 

  • Wesnes K, Warburton DM (1984) Effects of scopolamine and nicotine on human rapid information processing performance. Psychopharmacology 82:147–150

    Google Scholar 

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Authors and Affiliations

  1. Experimental Psychology, University of Sussex, BN1 9QG, Brighton, UK

    T. Duka

  2. Research Laboratories Schering AG, D-13342, Berlin, Germany

    H. Ott, A. Rohloff & B. Voet

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  1. T. Duka
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  2. H. Ott
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  3. A. Rohloff
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  4. B. Voet
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Duka, T., Ott, H., Rohloff, A. et al. The effects of a benzodiazepine receptor antagonist β-carboline ZK-93426 on scopolamine-induced impairment on attention, memory and psychomotor skills. Psychopharmacology 123, 361–373 (1996). https://doi.org/10.1007/BF02246647

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  • DOI: https://doi.org/10.1007/BF02246647

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