Abstract
Preclinical efforts to detect and characterize potential cognition enhancers appear to have been dominated by a strategy of demonstrating a wide variety of apparently beneficial behavioral effects with little attention given to the specific psychological mechanisms underlying behavioral enhancement. In particular, the question of whether or not behavioral facilitation is based on relevant mnemonic mechanisms and is independent of the stimulus properties and/or the motivational and attentional components of a task is not often considered. As a result, an overwhelming number of compounds have failed to produce the clinical effects predicted for them on the basis of preclinical research. The available data suggest that a more successful approach requires deductive research strategies rather than the indiscriminate accumulation of apparently beneficial effects in a variety of behavioral tasks and animal models. The first step towards such an approach is a systematic and rigorous evaluation of the different aspects of validity for the models most frequently used in preclinical research. It is concluded that a combination of good construct validity and good face validity represents a necessary condition for screening tests with predictive validity, and that the most popular paradigms fail to fulfil these criteria. Future screening programs for cognition enhancers will probably be characterized by a depreciation of “fast and dirty tests” in favor of approaches focussing on the validity of the effects of potential cognition enhancers.
Similar content being viewed by others
References
Bagne CA, Pomara N, Crook T, Gershon S (1986) Alzheimer's disease: strategies for treatment and research. In: Crook T, Bartus R, Ferris S, Gershon S (eds) Treatment development strategies for Alzheimer's disease. Mark Powley, Madison, pp 585–638
Barnas C, Miller C, Gunther V, Fleischhacker W (1987) Treatment of alcohol organic mental disorder with piracetam. Progr Neuropsychopharmacol Biol Psychiatry 11:729–737
Barnes JM, Costall B, Coughlan J, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ, Onaivi ES, Tomkins DM, Tyers MB (1990) The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates. Pharmacol Biochem Behav 35:955–962
Barondes SH (1969) Cerebral protein synthesis inhibitors block long term memory. Int Rev Neurobiol 12:177–205
Barraco RA, Stettner LJ (1976) Antibiotics and memory. Psychol Bull 2:242–302
Bartus RT (1978) Evidence for a direct cholinergic involvement in the scopolamine-induced amnesia in monkeys: effects of concurrent administration of physostigmine and methylphenidate with scopolamine. Pharmacol Biochem Behav 9:833–836
Bartus RT (1988) The need for common perspectives in the development and use of animal models for age-related cognitive and neurodegenerative disorders. Neurobiol Aging 9:445–451
Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417
Beatty WW, Butters N, Janowski DS (1986) Patterns of memory failure after scopolamine treatment: implications for cholinergic hypotheses of dementia. Behav Neural Biol 45:196–211
Becker RE, Giacobini E (1988) Mechanisms of cholinesterase inhibition in senile dementia of the Alzheimer type: clinical, pharmacological, and therapeutic aspects. Drug Dev Res 12:163–195
Beninger RJ (1989) Methods for determining the effects of drugs on learning. In: Boulton AA, Baker GB, Greenshaw AJ (eds) Neuromethods. Psychopharmacology, vol 13. Humana Press, Clifton, pp 623–685
Biegon A, Greenberger V, Segal M (1986) Quantitative histochemistry of brain acetylcholinesterase and learning rate in the aged rat. Neurobiol Aging 7:215–217
Bruno G, Mohr E, Gillespie M, Fedio P, Chase TN (1986) Muscarinic agonist therapy of Alzheimer's disease: a clinical trial of RS-86. Arch Neurol 43:659–661
Byrne J, Arie T (1989) Tetrahydroaminoacridine (THA) in Alzheimer's disease. BMJ 298:845–846
Caine ED (1980) Cholinomimetic treatment fails to improve memory disorders. N Engl J Med 303:585–586
Caltagirone C, Gainotti C, Masullo O (1982) Oral administration of chronic physostigmine does not improve cognitive or mnesic performances in Alzheimer's presenile dementia. Int J Neurosci 16:247–249
Chatelier G, Lacomblez L, et al (1990) Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer's type: a multicentre trial. BMJ 300:495–499
Chouinard G, Annable L, Ross-Chouinard A, Olivier M, Fontaine F (1983) Piracetam in elderly psychiatric patients with mild diffuse cerebral impairment. Psychopharmacology 81:100–106
Christie JE, Shering A, Ferguson J, Glem AIM (1981) Physostigmine and arecoline: effects of intravenous infusions in Alzheimer presenile dementia. Br J Psychiatry 138:46–50
Claus JJ, Ludwig C, Mohr E, Giuffra M, Blin J, Chase TN (1991) Nootropic drugs in Alzheimer's disease: symptomatic treatment with pramiracetam. Neurology 41:570–574
Collerton D (1986) Cholinergic function and intellectual decline in Alzheimer's disease. Neuroscience 19:1–28
Cumin R, Bandle EF, Gamzu E, Haefely, WE (1982) Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Psychopharmacology 78:104–111
Davidson M, Zemishlany Z, Mohs RC, Horvath TB, Powchik P, Blass JP, Davis KL (1988) 4-Aminopyridine in the treatment of Alzheimer's disease. Biol Psychiatry 23:485–490
Davis B, Andrewes D, Stargatt R, Ames D, Tuckwell V, Davis S (1990) Tetrahydroaminoacridine in Alzheimer's disease. Int J Geriat Psychiatry 5:317–321
Davis JW, Thomas RK, Adams HE (1971) Interactions of scopolamine and physostigmine with ECS and one trial learning. Physiol Behav 6:219–222
Davis KL, Hollander E, Davidson M, Davis BM, Mohs RC, Horvath TB (1987) Induction of depression with oxotremorine in patients with Alzheimer's disease. Am J Psychiatry 144:468–471
Deacon RMJ, Budhram P, Dawson D, Galliani G, Guy AP, Gardner CR (1990) Investigation of potential cognition enhancing properties of RU 33965, a benzodiazepine receptor partial inverse agonist. Psychopharmacology 101 [suppl]:45
Dean RL, Bartus RT (1988) Behavioral models of aging in nonhuman primates. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Psychopharmacology of the aging nervous system, vol 20. Plenum Press, New York, pp 325–392
Dekker JAM, Connor DJ, Thal LJ (1991) The role of cholinergic projections from the nucleus basalis in memory. Neurosci Biobehav Rev 15:299–317
DeNoble VJ, Repetti SJ, Gelpke, LW, Wood LM, Keim KL (1986) Vincopetine: nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav 24:1123–1128
Devanand DP, Sackeim HA, Brown RP, Mayeux R (1989) A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer's disease. Arch Neurol 46:854–857
Dokla CPJ, Thal LJ (1988) Effect of cholinesterase inhibitors on Morris water task behavior following lesions of the nucleus basalis magnocellularis. Behav Neurosci 102:861–871
Dokla CPJ, Parker SC, Thal LJ (1989) Tetrahydroaminoacridine facilitates passive avoidance learning in rats with nucleus basalis magnocellularis lesions. Neuropharmacology 11:1279–1282
Duka T, Stephens DN, Krause W, Dorow R (1987) Human studies on the benzodiazepine receptor antagonist β-carboline ZK 93 426: preliminary observations on psychotropic activity. Psychopharmacology 93:421–427
Duka T, Edelmann V, Schütt B, Dorow R (1988) β-Carboniles as tools in memory research: human data with the β-carboline ZK 93 426. In: Hindmarch I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Springer, Berlin Heidelberg New York, pp 246–260
Duncan CP (1949) The retroactive effect of electroshock on learning. J Comp Physiol Psychol 42:32–44
Essman WB (1971) Drug effects and learning and memory processes. Adv Pharmacol Chemother 9:241–330
Fisher A, Brandeis R, Pittel Z, Karton I, Sapir M, Dachir S, Levy A, Heldman E (1989) (+/-)-cis-2-methyl-spiro (1,3-oxathiolane-5,3') guinuclidine (AF102B): a new M1 agonist attenuates cognitive dysfunctions in AF64A treated rats. Neurosci Lett 102:325–331
Fitten LJ, Perryman KM, Gross PL, Fine H, Cummins J, Marshall C (1990) Treatment of Alzheimer's disease with short- and long-term oral THA and lecithin: a double-blind study. Am J Psychiatry 147:239–242
Flicker C, Serby M, Ferris SH (1990) Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed. Psychopharmacology 100:243–250
Flood JF, Cherkin A (1986) Scopolamine effects on memory retention in mice: A model for dementia? Behav Neural Biol 45:169–184
Flood JF, Vidal D, Bennett EL, Orme AE, Vasquez S, Jarvik ME (1978) Memory facilitation and anti-amnesic effects of corticosteroids. Pharmacol Biochem Behav 8:81–87
Forsyth DR, Surmon DJ, Morgan RA, Wilcock GK (1989) Clinical experience with side effects of tacrine hydrochloride in Alzheimer's disease: a pilot study. Age Ageing 18:223–229
Foster NL, Aldrich MS, Bluemlein L, White RF, Berent S (1989) Failure of cholinergic agonist RS-86 to improve cognition and movement in PSP despite effects on sleep. Neurology 39:257–261
Freedman LS, Judge ME, Quartermain D (1982) Effect of cycloheximide, a protein synthesis inhibitor, on mouse brain catecholamine biochemistry. Pharmacol Biochem Behav 17:187–191
Gash DM, Thomas GH (1983) What is the importance of vasopressin in memory processes? TINS 6:197–198
Gauthier S, Bouchard R, Lamontagne A, Bailey P, Bergman H, Ratner J, Tesfaye Y, Saint-Martin M, Bacher Y, Carrier L, Charbonneau R, Clarfield AM, Collier B, Dastoor D, Gauthier L, Germain M, Kissel C, Krieger M, Kushnir S, Masson H, Morin J, Nair V, Neirink L, Suissa S (1990) Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate stage Alzheimer's disease. N Engl J Med 322:1272–1276
Gauthier S, Bouchard R, Bacher Y, Bailey P, Bergman H, Carrier L, Carbaonneau R, Clarfield M, Bollier B, Dastorr D, Gauthier L, Germain M, Kissel M, Krieger M, Kushnir S, Lamontagne A, Morin J, Nair NPV, Neirinck L, Ratner J, St-Martin M, Suissa S, Tesfaye Y (1989) Progress report on the Canadian multicentre trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Can J Neurol Sci 16:543–546
Geula C, Mesulam MM (1989) Cortical cholinergic fibers in aging and Alzheimer's disease: a morphometric study. Neuroscience 33:469–481
Growdon JH, Corkin S, Huff FJ, Rosen TJ (1986) Piracetam combined with lecithin in the treatment of Alzheimer's disease. Neurobiol Aging 7:269–276
Hagan JJ, Morris RGM (1988) The cholinergic hypothesis of memory: a review of animal experiments. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Psychopharmacology of the aging nervous system, vol 20. Plenum Press, New York, pp 237–232
Hagan JJ, Jansen JHM, Broekkamp CLE (1989) Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics. Psychopharmacology 98:347–356
Hagan JJ, Jansen JHM, Nefkens FEW, de Boer T (1990) Therapeutic effect of THA on hemicholinium-3 induced learning impairment is dependent of serotonergic and noradrenergic systems. Psychopharmacology 101:376–383
Handelmann GE, Nevins ME, Mueller LL, Arnolde, SM, Cordi AA (1989) Milacemide, a glycine prodrug, enhances performance of learning tasks in normal and amnesic rodents. Pharmacol Biochem Behav 34:823–828
Harbaugh RE, Reeder TM, Senter HJ, Knopman DS, Raskin DS, Pirozzolo F, Chang-Chui H, Shetter AG, Bakay RAE et al. (1989) Intracerebroventricular bethanecol chloride infusion in Alzheimer's disease. J Neurosurg 71:481–486
Haroutunian V, Kanof PD, Davis K (1985) Pharmacological alleviation of cholinergic lesion induced memory deficits in rats. Life Sci 37:945–952
Haroutunian V, Kanof PD, Tsuboyama GK, Campbell GA, Davis KL (1986) Animal models of Alzheimer's disease: behavior, pharmacology, transplants. Can J Neurol Sci 13:385–393
Haroutunian V, Kanof PD, Tsuboyama GK, Campbell GA, Davis KL (1990a) Restoration of cholinomimetic activity by clonidine in cholinergic plus adrenergic lesioned rats. Brain Res 507:261–266
Haroutunian V, Mantin R, Kanof PD (1990b) Frontal cortex as the site of action of physostigmine in nBM lesioned rats. Physiol Behav 47:203–206
Heise GA (1984) Behavioral methods for measuring effects of drugs on learning and memory in animals. Med Res Rev 4:534–558
Henderson VW, Roberts E, Wimer C, Bardolph EL, Chui HC, Damasio AR, Eslinger PJ, Goldstein MF, Schneider LS, Teng EL, Tune LE, Weiner LP, Whitehouse PJ (1989) Multicenter trial of naloxone in Alzheimer's disease. Ann Neurol 25:404–406
Hinde RA (1976) The use of differences and similarities in comparative psychopathology. In: Serban G, Kling A (eds) Animal models in human psychobiology. Plenum Press, New York, pp 187–202
Hock FJ, McGaugh JL (1985) Enhancing effects of Hoe 175 on memory in mice. Psychopharmacology 86:114–117
Hock FJ, Gerhards HJ, Wiemer G, Stechl J, Rüger W, Urbach H (1989) Effects of the novel compound, Hoe 065, upon impaired learning and memory in rodents. Eur J Pharmacol 171:79–85
Hodges H, Ribeiro AM, Gray JA, Marchbanks RM (1990) Low dose tetrahydroaminoacridine (THA) improves cognitive function but does not affect brain acetylcholine in rats. Pharmacol Biochem Behav 36:291–298
Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioral effects of nimodipine in animals. Drug Res 32:347–360
Hollander E, Davidson M, Mohs RC, Horvath TB, Davis BM, Zemishlany Z, Davis KL (1987) RS 86 in the treatment of Alzheimer's disease: cognitive and biological effects. Biol Psychiatry 22:1067–1078
Höhmann CF, Antuono P, Coyle JT (1988) Basal forebrain cholinergic neurons and Alzheimer's disease. In: Iversen LI, Snyder SH, Iversen SD (eds) Handbook of psychopharmacology. Plenum Press, New York, pp 69–106
Huff FJ, Mickel SF, Corkin S, Growdon JH (1988) Cognitive functions affected by scopolamine in Alzheimer's disease and normal aging. Drug Dev Res 12:271–278
Izquierdo I (1989) Different forms of post-training memory processing. Behav Neural Biol 51:171–202
Janssen PAJ (1964) Screening tests and prediction from animals to man. In: Steinberg H (ed) Animal behavior and drug action. Little, Brown, Boston, pp 264–268
Jensen LH, Stephens DN, Sarter M, Petersen EN (1987) Bidirectional effects of β-carbolines and benzodiazepines on memory processes. Brain Res Bull 19:359–364
Jones DNC, Carey GJ, Costall B, Domeney AM, Gerrard PA, Naylor RJ, Tyers MB (1990) Arecoline and ondansetron reverse scopolamine-induced deficits in an object discrimination task in the marmoset. Psychopharmacology 101 [suppl]:99
Kameyama T, Nabeshima T, Noda Y (1986) Cholinergic modulation of memory for step down type passive avoidance task in mice. Res Communic Psychol Psychiatr Behav 2:193–206
Kawajiri S, Sakurai T, Ojima H, Hatanaka S, Yamasaki T, Kojima H, Akashi A (1988) Effect of DM-9384, a new pyrrolidone derivative, on learning behavior and cerebral choline acetyltransferase activity in rats. Psychopharmacology 96 [suppl]:306
Kelly PH, Enz A, Amstutz R (1990) Effects of cholinergic agents in a new two-trail swim test of exploration and memory formation. Psychopharmacology 102 [suppl]:104
Kolb B, Whishaw IQ (1990) Fundamentals of human neuropsychology. W.H. Freeman, New York
Kopelman MD, Corn TH (1988) Cholinergic “blockade” as a model for cholinergic depletion. A comparison of the memory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome. Brain 111:1079–1110
Kwo-On-Yuen PF, Mandel R, Chen AD, Thal LJ (1990) Tetrahydroaminoacridine improves the spatial deficit produced by nucleus basalis lesions in rats. Expl Neurol 108:221–228
Lal H, Kumar B, Forster MJ (1988) Enhancement of learning and memory in mice by a benzodiazepine receptor antagonist. FASEB J 2:2707–2711
Levin ED (1988) Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats. Behav Neural Biol 50:240–245
Maho C, Dutrieux G, Ammassari-Teule M (1988) Parallel modifications of spatial memory performance, exploration patterns and hippocampal theta rhythms in fornix damaged rats: reversal by oxotremorine. Behav Neurosci 102:610–604
Mandel RJ, Thal LJ (1988) Physostigmine improves water maze performance following nucleus basalis magnocellularis lesions in rats. Psychopharmacology 96:421–425
Markstein R (1989) Pharmacological approaches in the treatment of senile dementia. Eur Neurol 29:33–41
Martinez JL, Jensen RA, McGaugh JL (1981) Attenuation of experimentally-induced amnesia. Prog Neurobiol 16:155–186
Mastropaolo J, Nadi NS, Ostrowski NL, Crawley JN (1988) Galanin antagonizes acetylcholine on a memory task in basal forebrain lesioned rats. Proc Natl Acad Sci USA 85:9841–9845
McGaugh JL (1989a) Dissociating learning and performance: drug and hormone enhancement of memory storage. Brain Res Bull 23:329–345
McGaugh JL (1989b) Involvement of hormonal and neuromodulatory systems in the regulation of memory storage. Annu Rev Neurosci 12:255–287
McGaugh JL, Gold PE (1976) Modulation of memory by electrical stimulation of the brain. In: Rosenzweig MR, Bennett EL (eds) Neural mechanisms of learning and memory. MIT Press, Cambridge, pp 549–560
McGurk SR, Levin ED, Butcher LL (1988) Cholinergic-dopaminergic interactions in radial-arm maze performance. Behav Neural Biol 49:234–239
McKinney WT, Bunney WE (1969) Animal model of depression: review of evidence and implications for research. Arch Gen Psychiatry 21:240–248
Miyamoto M, Narumi S, Nagaoka A, Coyle JT (1989) Effects of continuous infusion of cholinergic drugs on memory impairment in in rats with basal forebrain lesions. J Pharmacol Exp Ther 248:825–835
Mohr E, Schlegel J, Fabbrini G, Williams J, Mouradian MM, Mann UM, Clauss JJ, Fedio P, Chase TN (1989) Clonidine treatment of Alzheimer's disease. Arch Neurol 46:376–378
Molchan SE, Mellow AM, Lawlor BA, Weingartner HJ, Cohen RM, Cohen MR, Sunderland T (1990) TRH attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 100:84–89
Molloy DW, Cape RDT (1989) Acute effects of oral pyridostigmine on memory and cognitive function in SDAT. Neurobiol Aging 10:199–204
Moos WH, Davis RE, Schwartz RD, Gamzu EK (1988) Cognition activators. Med Res Rev 8:353–391
Mouradian MM, Mohr E, Williams JA, Chase TN (1988) No response to high dose muscarinic agonist therapy in Alzheimer's disease. Neurology 38:606–608
Murray CL, Fibiger HC (1985) Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine. Neuroscience 14:1025–1032
Murray CL, Fibiger HC (1986) Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis. Behav Neurosci 100:23–32
Nabeshima T, Yoshida S, Kameyama T (1988a) Effects of the novel compound NIK-247 on impairment of passive avoidance response in mice. Eur J Pharmacol 154:263–269
Nabeshima T, Noda Y, Kameyama T (1988b) GABAergic modulation of memory with regard to passive avoidance and conditioned suppression tasks in mice. Psychopharmacology 94:69–73
Nabeshima T, Noda Y, Tohyama K, Ithoh J, Kameyama T (1990a) Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions. Eur J Pharmacol 178:143–149
Nabeshima T, Tohyama K, Ichihara K, Kameyama T (1990c) Attenuation of benzodiazepine-induced passive avoidance deficit by post-training administration of muscimol: interaction with the cholinergic neuronal system. Eur J Pharmacol 182:555–560
Nabeshima T, Tohyama K, Kameyama T (1990b) Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice. Pharmacol Biochem Behav 36:233–236
Nabeshima T, Tohyama K, Murase K, Ishihara S, Kameyama T, Yamsaki T, Hatanaka S, Kojima H, Sakurai T, Takasu Y, Shiotani T (1991) Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic rerceptors induced by cycloheximide. J Pharmacol Exp Ther 257:271–275
Nakahara N, Iga Y, Saito Y, Mizobe F, Kawanishi G (1989) Beneficial effects of FKS-508 (AF102B), a selective M1 agonist, on impaired working memory in AF64A treated rats. Jpn J Pharmacol 51:539–547
Nakahara N, Fujise N, Kawanishi G, Mizobe F (1990) Central muscarinic activities of an M1-selective agonist: preferential effect on reversal of amnesia. Brain Res 507:172–175
Newhouse PA, Sunderland T, Tariot PN, Blumhardt CL, Weingartner H, Mellow A, Murphy DL (1988) Intravenous nicotine in Alzheimer's disease: a pilot study. Psychopharmacology 95:171–175
Nicholson CD (1990) Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharmacology 101:147–159
Nyback H, Nyman H, Nordgren I, Lindstrom B (1988) Preliminary experiences and results with THA for the amelioration of symptoms of Alzheimer's disease. In: Giacobini E, Becker R (eds) Current research in Alzheimer's therapy. Taylor and Francis, New York, pp 231–236
Okazaki Y, Natori K, Irie T, Katsube J (1990) Effect of a novel CNS-selective cholinesterase inhibitor, SM-10888, on habituation and passive avoidance responses in mice. Jpn J Pharmacol 53:211–220
Palmer AM, Francis PT, Benton JS, Sims NR, Mann DMA, Neary D, Snowdon JS, Bowen DM (1987a) Presynaptic serotonergic dysfunction in patients with Alzheimer's disease. J Neurochem 48:8–15
Palmer AM, Francis PT, Bowen DM, Benton JS, Neary D, Mann DMA, Snowdon JS (1987b) Catecholaminergic neurons assessed ante-mortem in Alzheimer's disease. Brain Res 414:365–375
Parsons DS, Peagler A, Barlow TS, Harrell LE (1987) Failure of chronic physostigmine to ameliorate working memory deficits after medial septal lesions. Exp Neurol 96:456–461
Perry EK (1988) The cholinergic hypothesis-ten years on. Br Med Bull 42:63–69
Piercey MF, Vogelsang GD, Franklin SR, Tang AH (1987) Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces. Brain Res 424:1–9
Pontecorvo MJ, Evans HL (1985) Effects of aniracetam on delayed matching-to-sample performance of monkeys and pigeons. Pharmacol Biochem Behav 22:745–752
Porsolt RD (1989) The silent epidemic: the search for treatment of age-related memory impairment. TIPS 10:3–6
Poschel BPH (1988) New pharmacological perspectives on nootropic drugs. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Psychopharmacology of the aging nervous system, vol 20. Plenum Press, New York, pp 437–469
Procter AW, Lowe SL, Palmer AM, Francis PT, Esiri MM, Stratmann GC, Naijlerahim A, Patel AJ, Hunt A, Bowen DM (1988) Topographical distribution of neurochemical changes in Alzheimer's disease. J Neurol Sci 84:125–140
Quartermain D, Altman HJ (1982) Facilitation of retrieval byd-amphetamine following anisomycin-induced amnesia. Physiol Psychol 10:283–292
Randt CT, Judge ME, Bonnet KA, Quartermain D (1982) Brain cyclic AMP and memory in mice. Pharmacol Biochem Behav 17:677–680
Ridely RM, Baker HF, Drewett B, Johnson JA (1985) Effects of ibotenic acid lesions of the basal forebrain on serial reversal learning in marmosets. Psychopharmacology 86:438–443
Ridely RM, Murray TK, Johnson JA, Baker HF (1986) Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: modification cholinergic drugs. Brain Res 376:108–116
Ridely RM, Baker HF, Drewett B (1987) Effects of arecoline and pilocarpine on learning ability with marmosets pretreated with hemicholinium-3. Psychopharmacology 91:512–514
Ridely RM, Samson NA Baker HF, Johnson JA (1988) Visuospatial learning impairment following lesion of the cholinergic projection to the hippocampus. Brain Res 456:71–87
Riekkinen P, Sirvio J, Riekkinen P (1990) The effects of THA on medial septal lesion induced memory deficits. Pharmacol Biochem Behav 36:237–241
Robbins TW (1988) Arresting memory decline. Nature 336:207–208
Robinson DS, Kurtz NM (1986) A scientific and pharmaceutical industry perspective. In: Crook T, Bartus R, Ferris S, Gershon S (eds) Treatment development strategies of Alzheimer's disease. Mark Powley, Madison, pp 655–670
Rogers DC, Ballard TM, Hunter AJ, Hill RG (1990) Comparison of the effects of scopolamine and tacrine in the Morris water maze and delayed non-matching to sample task. Psychopharmacology 101 [suppl]:186
Rupniak NMJ, Steventon MJ, Field MJ, Jennings CA, Iversen SD (1989) Comparison of the effects of four cholinomimetics agents on cognition in primates following disruption by scopolamine or by lists of objects. Psychopharmacology 99:189–195
Rush DK (1986) Reversal of scopolamine-induced amnesia of passive avoidance by pre- and post-training naloxone. Psychopharmacology 89:296–300
Russell RW (1964) Extrapolation from animals to man. In: Steinberg H (ed) Animal behavior and drug action. Churchill, London, pp 410–418
Sahakian BJ, Jones G, Levy R, Gray J, Warburton D (1989) The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry 154:797–800
Sahgal A (1984) A critique of the vasopressin-memory hypothesis. Psychopharmacology 83:215–228
Sansone M, Castellano C, Battaglia M, Ammassari-Teule M (1990) Oxiracetam prevents mecamylamide-induced impairment of active, but not passive, avoidance learning in mice. Pharmacol Biochem Behav 36:389–392
Santucci AC, Kanof PD, Haroutunian V (1989) Effect of physostigmine on memory consolidation and retrieval processes in intact and nucleus basalis-lesioned rats. Psychopharmacology 99:70–74
Sara SJ (1980) Memory retrieval deficits: alleviation by etiracetam, a nootropic drug. Psychopharmacology 68:235–241
Sarter M, Steckler T (1989) Spontaneous exploration of a 6-arm radial tunnel maze by basal forebrain lesioned rats: effects of the benzodiazepine receptor antagonist β-carboline ZK 93 426. Psychopharmacology 98:193–202
Sarter M, Stephens DN (1988) β-carbolines as tools in memory research: animal data and speculations. In: Hindmarch I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Springer, Berlin Heidelberg New York, pp 230–245
Sarter M, Stephens DN (1989) Disinhibitory properties of β-carboline antagonists of benzodiazepine receptors: a possible therapeutic approach for senile dementia? Biochem Trans 17:81–83
Sarter M, Bodewitz G, Stephens DN (1988) Attenuation of the scopolamine-induced impairment in spontaneous alternation behavior by antagonist but not inverse agonist and agonist β-carbolines. Psychopharmacology 94:491–495
Sarter M, Bruno JP, Dudchenko P (1990) Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. Psychopharmacology 101:1–17
Schindler U, Rush DK, Fielding S (1984) Nootropic drugs: Animal models for studying effects on cognition. Drug Dev Res 4:567–576
Shutske GM, Pierrat FA, Cornfeldt ML, Szewczak MR, Huger FP, Bores GM, Haroutunian V, Davis KL (1988) (+/-)-9-amino-1,2,3,4-tetrahydroacridin-1-ol. A potential Alzheimer's disease therapeutic of low toxicity. J Med Chem 31:1278–1279
Spanis CW, Squire LR (1978) Elevation of brain tyrosine by hibitors of protein synthesis is not responsible for their amnesic effect. Brain Res 139:384–388
Spear NE, Miller JS, Jagielo JA (1990) Animal memory and learning. Annu Rev Psychol 41:169–211
Spignoli G, Pepeu G (1987) Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine. Pharmacol Biochem Behav 27:491–495
Squire LR, Slater PC, Miller PL (1975) Retrograde amnesia: temporal gradient in very long-term memory following electroconvulsive therapy. Science 187:77–79
Stephens DN, Sarter M (1988) Bidirectional nature of benzodiazepine receptor ligands extends to effects in vigilance. In: Hindmarch I, Ott H (eds) Benzodiazepine receptor ligands, memory and information processing. Springer, Berlin Heidelberg New York, pp 205–217
Stone WS, Croul CE, Gold PE (1988) Attenuation of scopolamine-induced amnesia in mice. Psychopharmacology 96:417–420
Strong R, Hicks P, Hsu L, Bartus RT, Enna SJ (1980) Age-related alterations in the rodent brain cholinergic system and behavior. Neurobiol Aging 1:59–63
Summers WK, Viesselamn JO, Marsh GM, Candelora K (1981) Use of THA in treatment of Alzheimer-like dementia: pilot study in twelve patients. Biol Psychiatry 16:145–153
Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long term treatment of senile dementia, Alzheimer type. N Engl J Med 315:1241–1245
Sweeney JE, Höhman CF, Moran TH, Coyle JT (1988) A long acting cholinestrase inhibitor reverses spatial memory deficits in mice. Pharmacol Biochem Behav 31:141–147
Sweeney JE, Bachman ES, Coyle JT (1990) Effects of different doses of galanthamine, a long acting acetylcholinesterase inhibitor, on memory in mice. Psychopharmacology 102:191–200
Takashima A, Itoh S (1988) Effect of V-9-M, a peptide fragment derived from procholecystokinin, on memory processes in the rat. Can J Physiol Pharmacol 67:228–231
Tariot PN, Cohen RM, Welkowitz JA, Sunderland T, Newhouse PA, Murphy DL, Weingartner H (1988) Multiple-dose arecoline infusions in Alzheimer's disease. Arch Gen Psychiatry 45:901–905
Thal LJ, Dokla CPJ, Armstrong DM (1988) Nucleus basalis magnocellularis lesions: lack of biochemical and immunocytochemical recovery and affect of cholinesterase inhibitors on passive avoidance. Behav Neurosci 102:852–860
Thompson TL, Filley CM, Mitchell WD, Culig KM, LoVerde M, Byny RL (1990) Lack of hydergine in patients with Alzheimer's disease. N Engl J Med 323:445–458
Tilson HA, McLamb RL, Shaw S, Rogers BC, Pediaditakis P, Cook L (1988) Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents. Brain Res 438:83–94
Tobe A, Egawa M, Nagai R (1983) Effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on the scopolamine-induced deficit of spontaneous alternation behavior in rats. Jpn J Pharmacol 33:775–784
Ueki A, Miyoshi K (1989) Effects of cholinergic drugs on learning impairment in ventral globus pallidus lesioned rats. J Neurol Sci 90:1–21
Warburton DM, Wesnes K (1984) Drugs as research tools in psychology: cholinergic drugs and information processing. Neuropsychobiology 11:121–132
Wettstein A, Spiegel R (1984) Clinical trials with the cholinergic drug RS 86 in Alzheimer disease (AD) and senile dementia of the Alzheimer type (SDAT). Psychopharmacology 84:572–573
Willner P (1984) The validity of animal models of depression. Psychopharmacology 83:1–16
Willner P (1986) Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case. Progr Neuropsychopharmacol Biol Psychiatry 10:677–690
Wolters ECh, Riekkinen P, Lowenthal A, Van der Plaats JJ, Zwart JMT, Sennef C (1990) DGAVP (Org 5667) in early Alzheimer's disease patients: an international double-blind, placebo-controlled, multicenter trial. Neurology 40:1099–1101
Yamamoto M, Shimizu M (1988) Effects of a new TRH analogue, YM-14673 on a passive avoidance test as a possible criterion of improvement in cognitive disturbance in rodents. Arch Pharmacol 338:262–267
Yamazaki N, Kato K, Kurihara E, Nagaoka A (1991) Cholinergic drugs reverse AF64A-induced impairment of passive avoidance learning in rats. Psychopharmacology 103:215–222
Zerbib R, Laborit H (1990) Chronic stress and memory: implication of the central cholinergic system. Pharmacol Biochem Behav 36:897–900
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sarter, M., Hagan, J. & Dudchenko, P. Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I. Psychopharmacology 107, 144–159 (1992). https://doi.org/10.1007/BF02245132
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245132