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Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification

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Abstract

The hypothesis that the cognitive decline in senile dementia is related to the loss of cortical cholinergic afferent projections predicts that pharmacological manipulations of the remaining cholinergic neurons will have therapeutic effects. However, treatment with cholinesterase inhibitors or muscarinic agonists has been, for the most part, largely unproductive. These drugs seem to disrupt the normal patterning of cholinergic transmission and thus may block proper signal processing. An alternative pharmacological strategy which focuses on the amplification of presynaptic activity without disrupting the normal patterning of cholinergic transmission appears to be more promising. Such a strategy may make use of the normal GABAergic innervation of basal forebrain cholinergic neurons in general, and in particular of the inhibitory hyperinnervation of remaining cholinergic neurons which may develop under pathological conditions. Disinhibition of the GABAergic control of cholinergic activity is assumed to intensify presynaptic cortical cholinergic activity and to enhance cognitive processing. Although the extent to which compounds such as the benzodiazepine receptor antagonistβ-carboline ZK 93 426 act via the basal forebrain GABA-cholinergic link is not yet clear, the available data suggest that the beneficial behavioral effects of this compound established in animals and humans are based on indirect cholinomimetic mechanisms. It is proposed that an activation of residual basal forebrain cholinergic neurons can be achieved most physiologically via inhibitory modulation of afferent GABAergic transmission. This modulation may have a therapeutic value in treating behavioral syndromes associated with cortical cholinergic denervation.

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References

  • Aigner TG, Mitchell SJ, Aggleton JP, DeLong MR, Struble RG, Price DL, Wenk GL, Mishkin M (1987) Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic acid lesions of the nucleus basalis of Meynert. Psychopharmacology 92:292–300

    Google Scholar 

  • Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopedal components of substantia innominata. Neuroscience 27:1–39

    Article  PubMed  Google Scholar 

  • Allen SJ, Dawbarn D, Wilcock GK (1988) Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer's disease. Brain Res 454:275–281

    Article  PubMed  Google Scholar 

  • Arendash GW, Millard WJ, Dunn AJ, Meyer EM (1987) Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat. Science 238:952–956

    Google Scholar 

  • Arendt T, Zvegintseva HG, Leontovich TA (1986) Dendritic changes in the basal nucleus of Meynert and in the diagonal band nucleus in Alzheimer's disease — a quantitative Golgi investigation. Neuroscience 19:1265–1278

    Article  PubMed  Google Scholar 

  • Atack JR, Perry EK, Bonham JR, Candy JM, Perry RH (1986) Molecular forms of acetylcholinesterase and butyrylcholinesterase in the aged human central nervous system. J Neurochem 47:263–277

    PubMed  Google Scholar 

  • Atweh S, Simon JR, Kuhar MJ (1976) Utilization of sodium-dependent high affinity choline uptake in vitro as a measure of the activity of cholinergic neurons in vivo. Life Sci 17:1535–1544

    Article  Google Scholar 

  • Avant GR, Speeg KV, Freemon FR, Schenker S, Berman ML (1979) Physostigmine reversal of diazepam-induced hypnosis. Ann Int Med 91:53–55

    PubMed  Google Scholar 

  • Bammer G (1982) Pharmacological investigations of neurotransmitter involvement in passive avoidance responding: a review and some new results. Neurosci Biobehav Rev 6:247–296

    Article  PubMed  Google Scholar 

  • Barnard E, Darlison MG, Seeburg P (1987) Molecular biology of the GABAA receptor: the receptor/channel superfamily. Trends Neurosci 10:502–509

    Article  Google Scholar 

  • Bartus RT, Dean RL, Pontecorvo MJ, Flicker C (1985) The cholinergic hypothesis: A historical overview, current perspective and future directions. In: Olton D, Gamzu E, Corkin S (eds) Memory dysfunctions: integration of animal and human research from clinical and preclinical perspectives. New York Academy of Sciences, New York, pp 332–358

    Google Scholar 

  • Bartus RT, Dean RL, Fisher SK (1986) Cholinergic treatment for age-related memory disturbances: Dead or barely coming of age? In: Crook T, Bartus RT, Ferris S, Gershon S (eds) Treatment development strategies for Alzheimer's disease. Mark Powley Assoc, Madison, pp 385–419

    Google Scholar 

  • Baud P, Mayo W, Le Moal M, Simon H (1988) Locomotor hyperactivity in the rat infusion of muscimol and [d-ala2]met-enkephalin into the nucleus basalis magnocellularis. Possible interaction with cortical cholinergic projections. Brain Res 452:203–211

    PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • Bigl V, Woolf NJ, Butcher LL (1982) Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: a combined fluorescent tracer and acetylcholinesterase analysis. Brain Res Bull 8:727–749

    Google Scholar 

  • Bird TD, Stranahan S, Sumi SM, Raskind M (1983) Alzheimer's disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups. Ann Neurol 14:284–293

    Article  PubMed  Google Scholar 

  • Blaker WD, Peruzzi G, Costa E (1984) Behavioral and neurochemical differentiation of specific projections in the septal-hippocampal cholinergic pathway of the rat. Proc Natl Acad Sci 81:1880–1882

    PubMed  Google Scholar 

  • Block RI, DeVoe M, Stanley B, Stanley M, Pomara N (1985) Memory performance in individuals with primary degenerative dementia: its similarity to diazepam-induced impairments. Exp Aging Res 11:151–155

    PubMed  Google Scholar 

  • Bonetti EP, Burkard WP, Gabl M, Hunkeler W, Lorez HP, Martin JR, Moehler W, Osterrieder W, Pieri L, Polc P, Richards JG, Schaffner R, Scherschlicht R, Schoch P, Haefely WE (1989) Ro 15-4513: partial inverse agonism at the BZR and interaction with ethanol. Pharmacol Biochem Behav 31:733–749

    Google Scholar 

  • Bowen DM, Smith CB, White P, Davison AN (1976) Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other brain atrophies. Brain 99:459–496

    PubMed  Google Scholar 

  • Braak H, Braak E (1986) Ratio of pyramidal cells versus non-pyramidal cells in the human frontal isocortex and changes in ratio with ageing and Alzheimer's disease. Prog Brain Res 70:185–212

    PubMed  Google Scholar 

  • Bradshaw CM, Sheridan RD, Szabadi E (1987) Involvement of M1-muscarinic receptors in the excitation of neocortical neurons by acetylcholine. Neuropharmacology 26:1195–1200

    Article  PubMed  Google Scholar 

  • Brady DR, Vaughn JE (1988) A comparison of the localization of choline acetyltransferase and glutamate decarboxylase immunoreactivity in rat cerebral cortex. Neuroscience 24:1009–1026

    Article  PubMed  Google Scholar 

  • Brinkman SD, Gershon S (1983) Measurement of cholinergic drug effects on memory in Alzheimer's disease. Neurobiol Aging 4:139–145

    Article  PubMed  Google Scholar 

  • Brioni JD, McGaugh JL (1988) Post-training administration of GABAergic antagonists enhances retention of aversively motivated tasks. Psychopharmacology 96:505–510

    Google Scholar 

  • 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

    PubMed  Google Scholar 

  • Buzsaki G, Bickford RG, Ponomareff G, Thal L, Mandel R, Gage H (1988) Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J Neurosci 8:4007–4026

    PubMed  Google Scholar 

  • Byrne J, Arie T (1989) Tetrahydroaminoacridine (THA) in Alzheimer's disease. Br Med J 298:845–846

    Google Scholar 

  • Caltagirone C, Gainotti C, Masullo O (1982) Oral administration of chronic physostigmine does not improve cognitive or mnestic performances in Alzheimer's presenile dementia. Int J Neurosci 16:247–249

    PubMed  Google Scholar 

  • Carew TJ (1970) Do passive avoidance tasks permit assessment of retrograde amnesia in rats? J Comp Physiol Psychol 72:267–271

    PubMed  Google Scholar 

  • Carey RJ (1987) Post-trial hormonal treatment effects: memory modulation or perceptual distortion? J Neurosci Meth 22:27–30

    Article  Google Scholar 

  • Casamenti F, Deffenu G, Abbamondi AL, Pepeu G (1986) Changes in cortical acetylcholine output induced by modulation of the nucleus basalis. Brain Res Bull 16:689–695

    Google Scholar 

  • Chan-Palay V (1988) Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer's and Parkinson's disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol 273:543–557

    Article  PubMed  Google Scholar 

  • Christie JE, Shering A, Ferguson J, Glem AIM (1981) Physostigmine and arecoline: effects of intravenous infusions in Alzheimer presenlie dementia. Br J Psychiat 138:46–50

    PubMed  Google Scholar 

  • Coleman PD, Flood DG (1986) Dendritic proliferation in the aging brain as a compensatory repair mechanism. Prog Brain Res 70:227–237

    PubMed  Google Scholar 

  • Collerton D (1986) Cholinergic function and intellectual decline in Alzheimer's disease. Neuroscience 19:1–28

    Article  PubMed  Google Scholar 

  • Consolo S, Ladinsky H, Peri G, Garattini S (1972) Effect of central stimulants and depressants on mouse brain acetylcholine and choline levels. Eur J Pharmacol 18:251–255

    Article  PubMed  Google Scholar 

  • Cosi C, Wood PL (1988) Lack of GABAergic modulation of acetylcholine turnover in the rat thalamus. Neurosci Lett 87:293–296

    Article  PubMed  Google Scholar 

  • Crawley JN (1985) Exploratory behavior models of anxiety in mice. Neurosci Biobehav Rev 9:37–44

    Article  PubMed  Google Scholar 

  • Crawley JN, Wenk GL (1989) Co-existence of galanin and acetylcholine: is galanin involved in memory processes and dementia? Trends Neurosci 12:278–281

    Article  PubMed  Google Scholar 

  • Crews FT, Meyer EM, Gonzales RA, Theiss C, Otero DH, Larson K, Raulli R, Calderini G (1986) Presynaptic and postsynaptic approaches to enhancing central cholinergic transmission. In: Crook T, Bartus RT, Ferris S, Gershon S (eds) Treatment development strategies for Alzheimer's disease. Mark Powley Assoc, Madison, pp 385–419

    Google Scholar 

  • Cummings JL, Benson DF (1987) The role of the nucleus basalis of Meynert in dementia: review and reconsideration. Alzheimer's Disease Assoc Disord1:128–145

    Google Scholar 

  • De Belleroche J, Gardiner IM, Hamilton MH, Birdsall NJM (1985) Analysis of muscarinic receptor concentration and subtypes following lesion of rat substantia innominata. Brain Res 340:201–209

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Donoghue JP, Carroll KL (1987) Cholinergic modulation of sensory responses in rat primary somatic sensory cortex. Brain Res 408:367–371

    Article  PubMed  Google Scholar 

  • Drachman DA, Sahakian BJ (1979) Effects of cholinergic agents on human learning and memory. In: Barbeau A, Growdon JH, Wurtman RJ (eds) Nutrition and the brain. Raven Press, New York, pp 351–365

    Google Scholar 

  • Drachman DA, Glosser G, Fleming P, Longenecker G (1982) Memory decline in the aged: treatment with lecithin and physostigmine. Neurology 32:944–950

    PubMed  Google Scholar 

  • Dreyfus CF, Bernd P, Martinez HJ, Rubin SJ, Black IB (1989) GABAergic and cholinergic neurons exhibit high-affinity nerve growth factor binding in rat basal forebrain. Exp Neurol 104:181–185

    Article  PubMed  Google Scholar 

  • Duka T, Stephens DN, Krause W, Dorow R (1987) Human 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 (1988)β-carbolines as tools in memory research: human data with theβ-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

    Google Scholar 

  • El-Defrawy SR, Coloma F, Jhamandas K, Boegman RJ, Beninger RJ, Wirsching BA (1985) Functional and neurochemical cortical cholinergic impairment following neurotoxic lesions of the nucleus magnocellularis in the rat. Neurobiol Aging 6:325–330

    Article  PubMed  Google Scholar 

  • Etherington R, Mittleman G, Robbins TW (1987) Comparative effects of nucleus basalis and fimbria-fornix lesions on delayed matching and alternation tests of memory. Neurosci Res Commun 1:135–143

    Google Scholar 

  • Everitt HJ, Robbins TW, Evenden JL, Marston HM, Jones GH, Sirkiä TE (1987) The effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on the acquisition and retention of a conditional discrimination: implications for cholinergic hypotheses of learning and memory. Neuroscience 22:441–469

    Article  PubMed  Google Scholar 

  • File SE, Pellow S (1986) Intrinsic actions of the benzodiazepine receptor antagonist Ro 15-1788. Psychopharmacology 88:1–11

    Google Scholar 

  • Fishman EB, Siek GC, MacCallum RD, Bird ED, Volicer L, Marquis JK (1986) Distribution of molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type. Ann Neurol 19:246–252

    PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

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

    Google Scholar 

  • Gardner CR (1988) Pharmacological profiles in vivo of benzodiazepine receptor ligands. Drug Dev Res 12:1–28

    Article  Google Scholar 

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

    Google Scholar 

  • Giorgi O, Corda MG, Fernandez A, Biggio G (1989) Theβ-carboline derivatives ZK 93 426 and FG 71 42 fail to precipitate abstinence signs in diazepam-dependent cats. Pharmacol Biochem Behav 32:671–675

    Google Scholar 

  • Grant SJ, Aston-Jones G (1986) Discharge properties of cortically projecting nucleus basalis neurons in behaving animals. Soc Neurosci 1986 (Abstract)

  • Hagan JJ, Jansen JHM, Broekkamp CLE (1989) Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics. Psychopharmacology 98:347–356

    Google Scholar 

  • Hallak M, Giacobini E (1989) Physostigmine, Tacrine and metrifonate: the effect of multiple doses on acetylcholine metabolism in rat brain. Neuropharmacology 28:199–206

    Article  PubMed  Google Scholar 

  • Hallanger AE, Wainer BH, Rye DB (1986) Colocalization of gamma-aminobutyric acid and acetylcholinesterase in rodent cortical neurons. Neuroscience 19:763–769

    Article  PubMed  Google Scholar 

  • Halliwell JV (1986) M-current in human neocortical neurons. Neurosci Lett 67:1–6

    Article  PubMed  Google Scholar 

  • Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res 250:71–92

    Article  PubMed  Google Scholar 

  • Hardy J, Adolfsson R, Alafuzoff I, Bucht G, Marcusson J, Nyberg P, Perdahl E, Wester P, Winblad B (1985) Transmitter deficits in Alzheimer's disease. Neurochem Int 7:545–563

    Article  Google Scholar 

  • Haroutanian V, Kanof P, Davis KL (1985) Pharmacological alleviation of cholinergic lesion induced memory deficits in rats. Life Sci 37:945–952

    Article  PubMed  Google Scholar 

  • Hartgraves SL, Mensah PL, Kelly PH (1982) Regional decreases of cortical choline acetyltransferase after lesions of the septal area and in the area of nucleus basalis magnocellularis. Neuroscience 7:2369–2376

    Article  PubMed  Google Scholar 

  • Hassler R (1938) Zur Pathologie der Paralysis agitans und des postenzephalitischen Parkinsonismus. J Psychol Neurol Lpz 48:387–476

    Google Scholar 

  • Helen P, London ED (1984) Muscimol-scopolamine interactions in the rat brain: a study with 2-deoxy-d-[1-14C]glucose. J Neurosci 4:1405–1413

    PubMed  Google Scholar 

  • Higitt A, Lader M, Fonagy P (1986) The effects of the benzodiazepine receptor antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects. Psychopharmacology 89:395–403

    PubMed  Google Scholar 

  • Hodges H, Trasher S, Gray JA (1989) Improved radial maze performance induced by the benzodiazepine antagonist ZK 93 426 in lesioned and alcohol treated rats. Behav Pharmacol 1:45–55

    Google Scholar 

  • Ingham CA, Bolam JP, Smith AD (1988) GABA-immunoreactive synaptic boutons in the rat basal forebrain: comparison of neurons that project to the neocortex with pallidosubthalamic neurons. J Comp Neurol 273:263–282

    Article  PubMed  Google Scholar 

  • Jensen LH, Petersen EN, Braestrup C, Honore T, Kehr W, Stephens DN, Schneider H, Seidelmann D, Schmiechen R (1984) Evaluation of theβ-carboline ZK 93 426 as a benzodiazepine receptor antagonist. Psychopharmacology 83:249–256

    Google Scholar 

  • Jensen LH, Stephens DN, Sarter M, Petersen EN (1987) Bidirectional effects ofβ-carbolines and benzodiazepines on memory processes. Brain Res Bull 19:359–364

    Google Scholar 

  • Kellar KJ, Whitehouse PJ, Martino-Barrows AM, Marcus K, Price DL (1987) Muscarinic and nicotinic cholinergic binding sites in Alzheimer's disease cerebral cortex. Brain Res 436:62–68

    Article  PubMed  Google Scholar 

  • Kumar BA, Forster MJ, Lal H (1988) CGS 8216, a benzodiazepine receptor antagonist, enhances learning and memory in mice. Brain Res 460:195–198

    Article  PubMed  Google Scholar 

  • Lal H, Kumar B, Forster MJ (1988) Enhancement of learning and memory in mice by a benzodiazepine anatagonist. FASEB J 2:2707–2711

    PubMed  Google Scholar 

  • Lamour Y, Dutar P, Rascol O, Jobert A (1986) Basal forebrain neurons projecting to the rat frontoparietal cortex: electrophysiological and pharmacological properties. Brain Res 362:122–131

    Article  PubMed  Google Scholar 

  • Lams BE, Isacson O, Sofroniew MV (1988) Loss of transmitter-associated enzyme staining following axotomy does not indicate death of brainstem cholinergic neurons. Brain Res 475:401–406

    Article  PubMed  Google Scholar 

  • Lister RG (1988) Partial reversals of ethanol-induced reductions in exploration by two benzodiazepine antagonists (flumazenil and ZK 93 426). Brain Res Bull 21:765–770

    Google Scholar 

  • Little HJ, Nutt DJ, Taylor SC (1987) Kindling and withdrawal changes at the benzodiazepine receptor. J Psychopharmacol 1:35–46

    Google Scholar 

  • Lorez H-P, Martin JR, Keller HH, Cumin R (1988a) Effect of aniracetam and the benzodiazepine receptor partial inverse agonist RO 15-3505 on cerebral glucose utilization and cognitive function after lesioning of cholinergic forebrain nuclei in the rat. Drug Dev Res 14:359–362

    Article  Google Scholar 

  • Lorez HP, von Frankenberg M, Weskamp G, Otten U (1988b) Effect of bilateral decortication on nerve growth factor content in basal nucleus and neostriatum of adult rat brain. Brain Res 454:355–360

    Article  PubMed  Google Scholar 

  • Lowe SL, Francis PT, Procter AW, Palmer AM, Davison AN, Bowen DM (1988) Gamma-aminobutyric acid concentration in brain tissue at two stages of Alzheimer's disease. Brain 111:785–799

    PubMed  Google Scholar 

  • Lundgren G, Nordgren I, Karlen B, Jacobson G (1987) Effects of diazepam on blood choline and acetylcholine turnover in brain of mice. Pharmacol Toxicol 60:96–99

    PubMed  Google Scholar 

  • Malatynska E, Knapp R, Ikeda M, Yamamura HI (1989)β-carboline interactions at the BZ-GABA receptor chloride-ionophore complex in the rat cerebral cortex. Brain Res Bull 22:845–848

    Article  PubMed  Google Scholar 

  • Mandel RJ, Thal JL (1988) Physostigmine improves water maze performance following nucleus basalis magnocellularis lesions in rats. Psychopharmacology 96:421–425

    Google Scholar 

  • Mann DMA, Yates P, Marcyniuk B (1984) A comparison of changes in the nucleus basalis and locus caeruleus in Alzheimer's disease. J Neurol Neurosurg Psychiatry 47:201–203

    PubMed  Google Scholar 

  • Mash DC, Potter LT (1986) Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain. Neuroscience 19:551–564

    Article  PubMed  Google Scholar 

  • Mash DC, Flynn DD, Potter LT (1985) Loss of M2 muscarinic receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 228:1115–1117

    Google Scholar 

  • McCormick DA, Prince DA (1986) Mechanisms of action of acetylcholine in the guinea-pig cerebral cortex, in vitro. J Physiol 375:169–194

    PubMed  Google Scholar 

  • McGeer PL, McGeer EG, Suzuki J, Dolman CE, Nagai T (1984) Aging, Alzheimer's disease, and the cholinergic system of the basal forebrain. Neurology 34:741–745

    PubMed  Google Scholar 

  • Messer WS, Ellerbrock B, Price M, Hoss W (1989) Autoradiographic analysis of agonist binding to muscarinic receptor subtypes. Biochem Pharmacol 38:837–850

    Article  PubMed  Google Scholar 

  • Metcalf RH, Boegman RJ, Quirion R, Riopelle RJ, Ludwin SK (1987) Effect of quinolinic acid in the nucleus basalis magnocellularis on cortical high-affinity choline uptake. J Neurochem 49:639–644

    PubMed  Google Scholar 

  • Metha AK, Ticku MJ (1989) Benzodiazepine and beta-carboline interactions with GABAA receptor-gated chloride channels in mammalian cultured spinal cord neurons. J Pharmacol Exp Ther 249:418–423

    PubMed  Google Scholar 

  • Metherate R, Weinberger NM (1989) Acetylcholine produces stimulus-specific receptive field alterations in cat auditory cortex. Brain Res 480:372–377

    Google Scholar 

  • Meyer EM, Otero DH (1985) Pharmacological and ionic characterizations of the muscarinic receptors modulating [3H]acetylcholine release from rat cortical synaptosomes. J Neurosci 5:1202–1207

    PubMed  Google Scholar 

  • Meyer EM, Arendash GW, Judkins JH, Ying L, Wade C, Kem WR (1987) Effects of nucleus basalis lesions on the muscarinic and nicotinic modulation of [3H]acetylcholine release in the rat cerebral cortex. J Neurochem 49:1758–1762

    PubMed  Google Scholar 

  • Miller JA, Chmielewski PA (1989) Effects of β-carbolines on high affinity choline uptake in cortical and hippocampal synaptosomes. Soc Neurosci 15:472.8 (Abstract)

    Google Scholar 

  • Miller JA, Richter JA (1986) Effects of GABAergic drugs in vivo on high-affinity choline uptake in vitro in mouse hippocampal synaptosomes. J Neurochem 47:1916–1918

    PubMed  Google Scholar 

  • Miyamoto M, Narumi S, Nagaoka A, Coyle JT (1989) Effects of continuous infusion of cholinergic drugs on memory impairments in rats with basal forebrain lesions. J Pharmacol Exp Ther 248:825–835

    PubMed  Google Scholar 

  • Mogensen GJ, Swanson LW, Wu M (1983) Neural projections from nucleus accumbens to globus pallidus, substantia innominata, and lateral preoptic-lateral hypothalamic area: an anatomical and electrophysiological investigation in the rat. J Neurosci 3:189–202

    PubMed  Google Scholar 

  • Mohs RC, Davis BM, Johns CA, Mathe AA, Greenwald BS, Horvath TB, Davis KL (1985) Oral physostigmine treatment of patients with Alzheimer's disease. Am J Psychiatry 142:28–33

    PubMed  Google Scholar 

  • Molloy DW, Cape RDT (1989) Acute effects of oral pyridostigmine on memory and cognitive function in SDAT. Neurobiol Aging 10:199–204

    Article  PubMed  Google Scholar 

  • Müller CM, Singer W (1989) Acetylcholine-induced inhibition in the cat visual cortex is mediated by a GABAergic mechanism. Brain Res 487:335–342

    Article  PubMed  Google Scholar 

  • Murray CL, Fibiger HC (1985) Learning and memory deficits after lesions of the nucleus basalis magnocellularis: reversal by physostigmine. Neurosci 14:1025–1032

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Nabeshima T, Noda Y, Kameyama T (1988) GABAergic modulation of memory with regard to passive avoidance and conditioned suppression tasks in mice. Psychopharmacology 94:69–73

    Google Scholar 

  • Nagel JA, Huston JP (1988) Enhanced inhibitory avoidance learning produced by post-trial injections of substance P into the basal forebrain. Behav Neural Biol 49:374–385

    Article  PubMed  Google Scholar 

  • Nagy J, Decsi L (1978) Physostigmine, a highly potent antidote for acute experimental diazepam intoxication. Neuropharmacology 17:469–475

    Article  PubMed  Google Scholar 

  • Nilsson L, Adem A, Hardy J, Winblad B, Nordberg A (1987) Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine in AD/SDAT brains via nicotinic receptors? J Neural Transm 70:357–368

    Article  PubMed  Google Scholar 

  • Nordberg A, Adem A, Hardy J, Winblad B (1988) Change in nicotinic receptor subtypes in temporal cortex of Alzheimer brains. Neurosci Lett 86:317–321

    Article  PubMed  Google Scholar 

  • Palacios JM, Bolliger G, Closse A, Enz A, Gmelin G, Malanowzki J (1986) The pharmacological assessment of RS 86 (2-ethyl-8-methyl-2,8-diazospiro-[4,5]-decan-1,3-dion hydrobromide): a potent, specific muscarinic acetylcholine receptor agonist. Eur J Pharmacol 125:45–62

    Article  PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Palmer AM, Wilcock GK, Esiri MM, Francis PT, Bowen DM (1987c) Monoaminergic innervation of the frontal and temporal lobes in Alzheimer's disease. Brain Res 401:231–238

    Article  PubMed  Google Scholar 

  • Patel S, Slater P (1988) Effects of GABA compounds injected into the subpallidal regions of rat brain on nucleus accumbens evoked hyperactivity. Behav Neurosci 102:596–600

    Article  PubMed  Google Scholar 

  • Perry EK (1986) The cholinergic hypothesis-ten years on. Br Med Bull 42:63–69

    PubMed  Google Scholar 

  • Perry EK, Blessed G, Tomlinson BE, Perry RH, Cow TJ, Cross AJ, Dockray GJ, Dimaline R, Arregui A (1981) Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes. Neurobiol Aging 2:251–256

    Article  PubMed  Google Scholar 

  • Perry EK, Atack JR, Perry RH, Hardy JA, Dodd PR, Edwardson JA, Blessed G, Tomlinson BE, Fairbairn AF (1984) Intralaminar neurochemical distributions in human midtemporal cortex: comparison between Alzheimer's disease and the normal. J Neurochem 42:1402–1410

    PubMed  Google Scholar 

  • Perry EK, Smith CJ, Court JA, Bonham JR, Rodway M, Atack JR (1988) Interaction of 9-amino-1,2,3,4-tetrahydroamino-acridine (THA) with human cortical nicotinic and muscarinic receptor binding in vitro. Neurosci Lett 91:211–216

    Article  PubMed  Google Scholar 

  • Phillis JW, Siemens PK, Wu PH (1980) Effects of diazepam on adenosine and acetylcholine release from rat cerebral cortex: further evidence for a purinergic mechanism in action of diazepam. Br J Pharmacol 70:341–348

    PubMed  Google Scholar 

  • Pirch JH, Corbus MJ, Ridgon GC, Lyness WH (1986) Generation of cortical event-related slow potentials in the rat involves nucleus basalis cholinergic innervation. EEG Clin Neurophysiol 63:464–475

    Article  Google Scholar 

  • Poherecki R, Head R, Domino EF (1988) Effects of selected muscarinic cholinergic antagonists on [3H]acetylcholine release from rat hippocampal slices. J Pharmacol Exp Ther 244:213–217

    PubMed  Google Scholar 

  • Polc P, Bonetti EP, Schaffner R, Haefely W (1982) A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers,β-carbolines, and phenobarbitone. Arch Pharmacol 321:260–264

    Article  Google Scholar 

  • Pomara N, Stanley M (1986) The functional status of central muscarinic receptors in Alzheimer's disease: assessments and therapeutic implications. In: Crook T, Bartus RT, Ferris S, Gershon S (eds) Treatment development strategies for Alzheimer's disease. Mark Powley Assoc, Madison, pp 451–472

    Google Scholar 

  • Preston GC, Ward C, Lines CR, Poppleton P, Haigh JRM, Traub M (1989) Scopolamine and benzodiazepine models of dementia: cross-reversals by Ro 15-1788 and physostigmine. Psychopharmacology 98:487–494

    Google Scholar 

  • Prince DA, Huguenard JR (1988) Functional properties of neocortical neurons. In: Rakic P, Singer W (eds) Neurobiology of neocortex. Wiley, New York, pp 153–176

    Google Scholar 

  • Pritzel M, Huston JP, Sarter M (1983) Behavioral and neuronal reorganization after unilateral substantia nigra lesions: evidence for increased interhemispheric nigrostriatal projections. Neuroscience 9:879–888

    Article  PubMed  Google Scholar 

  • Probst A, Cortes R, Ulrich J, Palcios JM (1988) Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer's disease: an autoradiographic study. Brain Res 450:190–201

    Article  PubMed  Google Scholar 

  • Procter AW, Bowen DM (1988)β-carbolines for Alzheimer's disease? — more evidence, a test of efficacy and some precautions. Trends Neurosci 11:208–209

    Article  PubMed  Google Scholar 

  • Procter AW, Lowe S, Palmer AM, Francis PT, Esiri MM, Stratmann GC, Najlerahim A, Patel AJ, Hunt A, Bowen DM (1988) Topographical distribution of neurochemical changes in Alzheimer's disease. J Neurol Sci 84:125–140

    Article  PubMed  Google Scholar 

  • Rasmusson DD, Dykes RW (1988) Long-term enhancement of evoked potentials in cat somatosensory cortex produced by co-activation of the basal forebrain and cutaneous receptors. Exp Brain Res 70:276–286

    Article  PubMed  Google Scholar 

  • Rasool CG, Svendsen CN, Selkoe DJ (1986) Neurofibrillary degeneration of cholinergic and noncholinergic neurons of the basal forebrain in Alzheimer's disease. Ann Neurol 20:482–488

    Article  PubMed  Google Scholar 

  • Raulli RE, Arendash G, Crews FT (1989) Effects of nbM lesions on muscarinic-stimulation of phosphoinositide hydrolysis. Neurobiol Aging 10:191–197

    Article  PubMed  Google Scholar 

  • Reiner PB, McGeer E (1988) THA increases action potential duration of central histamine neurons in vitro. Eur J Pharmacol 155:265–270

    Article  PubMed  Google Scholar 

  • Richards JG, Schoch P, Häring P, Takacs B, Möhler H (1987) Resolving GABAA/benzodiazepine receptors: Cellular and subcellular localization in the CNS with monoclonal antibodies. J Neurosci 7:1866–1886

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Ridley RM, Murray TK, Johnson JA, Baker HF (1986) Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: modification by cholinergic drugs. Brain Res 376:108–116

    Article  PubMed  Google Scholar 

  • Rigdon GC, Pirch JH (1984) Microinjections of procaine or GABA into the nucleus basalis magnocellularis affects cue-elicited unit responses in the rat frontal cortex. Exp Neurol 85:283–296

    Article  PubMed  Google Scholar 

  • Rigdon GC, Pirch JH (1986) Nucleus basalis involvement in conditioned neuronal responses in rat frontal cortex. J Neurosci 6:2535–2542

    PubMed  Google Scholar 

  • Rinne JO, Lönnberg P, Marjamäki P, Rinne UK (1989) Brain muscarinic receptor subtypes are differently affected on Alzheimer's disease and Parkinson's disease. Brain Res 483:402–406

    Article  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ, Ryan CN, Marston HM, Jones GH, Page KJ (1989) Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional discrimination: differential effects on cholinergic mechanisms. Neuroscience 28:337–352

    Article  PubMed  Google Scholar 

  • Rothman SM, Olney JW (1987) Excitotoxicity and the NMDA receptor. Trends Neurosci 10:299–302

    Article  Google Scholar 

  • Rylett RJ, Ball MJ, Colhoun EH (1983) Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease. Brain Res 289:169–175

    Article  PubMed  Google Scholar 

  • Sahakian B, 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

    PubMed  Google Scholar 

  • Sahgal A (1984) A critique of the vasopressin-memory hypothesis. Psychopharmacology 83:215–228

    Google Scholar 

  • Sarter M (1989) Elevations of local cerebral glucose utilization by theβ-carboline ZK 93 426. Eur J Pharmacol (in press)

  • Sarter M, Schneider HH (1988) High density of benzodiazepine binding sites in the substantia innominata of the rat. Pharmacol Biochem Behav 30:679–682

    Google Scholar 

  • Sarter M, Steckler T (1989) Spontaneous exploration of a 6-arm radial tunnel maze by basal forebrain lesioned rats: effects of the benzodiazepine receptor antagonistβ-carboline ZK 93 426. Psychopharmacology 98:193–202

    Google Scholar 

  • 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 Verlag, Berlin, pp 230–245

    Google Scholar 

  • Sarter M, Stephens DM (1989) Disinhibitory properties ofβ-carboline antagonists of benzodiazepine receptors: a possible therapeutic approach for senile dementia? Biochem Soc Transact 17:81–83

    Google Scholar 

  • Sarter M, Bodewitz G, Stephens DN (1988a) Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonistβ-carbolines. Psychopharmacology 94:491–495

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Sato H, Hata Y, Hagihara K, Tsumoto T (1987) Effects of cholinergic depletion ion neuron activities in the cat visual cortex. J Neurophysiol 58:781–794

    PubMed  Google Scholar 

  • Sato TN, Neale JH (1989) Type I and Type IIγ-aminobutyric acid/benzodiazepine receptors: purification and analysis of novel receptor complex from neonatal cortex. J Neurochem 52:1114–1122

    PubMed  Google Scholar 

  • Scarth BJ, Jhamandas K, Boegman RJ, Beninger RJ, Reynolds JN (1989) Cortical muscarinic receptor function following quinolinic acid-induced lesion of the nucleus basalis magnocellularis. Exp Neurol 103:158–164

    Article  PubMed  Google Scholar 

  • Scatton B, Bartholini G (1982)γ-aminobutyric acid (GABA) receptor stimulation. IV. Effect of progabide (SL 76002) and other GABAergic agents on acetylcholine turnover in rat brain areas. J Pharmacol Exp Ther 220:689–695

    PubMed  Google Scholar 

  • Sethy VA (1978) Effect of hypnotic and anxiolytic agents on regional concentration of acetylcholine in rat brain. Arch Pharmacol 301:157–161

    Article  Google Scholar 

  • Shreve PE, Uretsky NJ (1988) Effect of GABAergic transmission in the subpallidal region on the hypermotility response to the administration of excitatory amino acids and picrotoxin into the nucleus accumbens. Neuropharmacology 27:1271–1277

    Article  PubMed  Google Scholar 

  • Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DJ, Davison AN (1983) Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 40:503–509

    PubMed  Google Scholar 

  • Smith G (1988) Animal models of Alzheimer's disease: experimental cholinergic denervation. Brain Res Rev 13:103–118

    Article  Google Scholar 

  • 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

    Google Scholar 

  • Stern Y, Sano M, Mayeux R (1987) Effects of oral physostigmine in Alzheimer's disease. Ann Neurol 22:306–310

    Article  PubMed  Google Scholar 

  • Summers WK, Majovski LV, Marsh GM, Tachiki K, Kling A (1986) Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer-type. New Engl J Med 315:1241–1245

    PubMed  Google Scholar 

  • Sunderland T, Tariot PN, Newhouse PA (1988) Differential responsitivity of mood, behavior, and cognition to cholinergic agents in elderly neuropsychiatric populations. Brain Res Rev 13:371–389

    Article  Google Scholar 

  • Sunderland T, Weingartner H, Cohen RM, Tariot PN, Newhouse PA, Thompson KE, Lawlor BA, Mueller EA (1989) Low-dose oral lorazepam administration in Alzheimer subjects and age-matched controls. Psychopharmacology 99:129–133

    Google Scholar 

  • Supavilai P, Karobath M (1984) [35S]-t-butylbicyclophosphorothionate binding sites are constituents of theγ-aminobutyric acid benzodiazepine receptor complex. J Neurosci 4:1193–1200

    PubMed  Google Scholar 

  • Swanson LW, Cowan WM (1975) A note on the connections and development of the nucleus accumbens. Brain Res 92:324–330

    Article  PubMed  Google Scholar 

  • Tagliavini F, Pilleri G (1983) Basal nucleus of Meynert. A neuropathological study in Alzheimer's disease, simple senile dementia, Pick's disease and Huntington's chorea. J Neurol Sci 62:243–260

    Article  PubMed  Google Scholar 

  • Thal LJ, Fuld PA, Masur DM, Sharpless NS (1983) Oral physostigmine and lecithine improve memory in Alzheimer's disease. Ann Neurol 13:491–496

    Article  PubMed  Google Scholar 

  • Thal LJ, Dokla CPJ, Armstrong DM (1988) Nucleus basalis magnocellularis lesions: lack of effect of biochemical and immunocytochemical recovery and effect of cholinesterase inhibitors on passive avoidance. Behav Neurosci 102:852–860

    Article  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Turski WA, Cavalheiro EA, Coimbra C, da Penha Berzaghi M, Ikonomidou-Turski C, Turski L (1987) Only certain antiepileptic drugs prevent seizures induced by pilocarpine. Brain Res Rev 12:281–305

    Article  Google Scholar 

  • Ueki A, Miyoshi K (1989) Effects of cholinergic drugs on learning impairment in ventral globus pallidus-lesioned rats. J Neurol Sci 90:1–21

    Article  PubMed  Google Scholar 

  • Ulfig N (1988) Neuronal loss and GABAergic innervation in the basal forebrain. Trends Neurosci 11:209

    Article  PubMed  Google Scholar 

  • Ulus IH, Wurtman RJ, Mauron C, Blusztajn JK (1989) Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum. Brain Res 484:217–227

    Article  PubMed  Google Scholar 

  • Vatashsky E, Beilin B, Razin M, Weinstock M (1986) Mechanism of antagonism by physostigmine of acute flunitrazepam intoxication. Anesthesiology 64:248–252

    PubMed  Google Scholar 

  • Venault P, Chapouthier G, Prado de Carvalho L, Simiand J, Morre M, Dodd RH, Rossier J (1986) Benzodiazepine impairs andβ-carboline enhances performance in learning and memory tasks. Nature 321:864–866

    Article  PubMed  Google Scholar 

  • Vizi ES, Kobayashi O, Töröcsik A, Kinjo M, Nagashima H, Manabe N, Goldiner PL, Potter PE, Foldes FF (1989) Heterogeneity of presynaptic muscarinic receptors involved in modulation or transmitter release. Neuroscience 31:259–267

    Article  PubMed  Google Scholar 

  • Walaas I, Fonnum F (1979) The distribution and origin of glutamate decarboxylase and choline acetyltransferase in ventral pallidum and other basal forebrain structures. Brain Res 177:235–336

    Article  Google Scholar 

  • Watson M, Vickroy TW, Fibiger HC, Roeske WR, Yamamura HI (1985) Effects of bilateral ibotenate-induced lesions of the nucleus basalis magnocellularis upon selective cholinergic biochemical markers in the rat anterior cerebral cortex. Brain Res 346:387–391

    Article  PubMed  Google Scholar 

  • Wenk GL (1984) Pharmacological manipulations of the substantia innominata-cortical cholinergic pathway. Neurosci Lett 51:99–103

    Article  PubMed  Google Scholar 

  • Wettstein A, Speigel 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

    Google Scholar 

  • Whitehouse PJ, Price DJ, Clark AW, Coyle JT, DeLong MR (1981) Alzheimer's disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126

    Article  PubMed  Google Scholar 

  • Wisden W, Morris BJ, Darlison MG, Hunt SP, Barnard EA (1989) Localization of GABAA receptorα-subunit mRNAs in relation to receptor subtypes. Mol Brain Res 5:305–310

    Article  PubMed  Google Scholar 

  • Wolkowitz OM, Weingartner H, Thompson K, Pickar D, Paul SM, Hommer DW (1987) Diazepam-induced amnesia: a neuropharmacological model of “organic amnestic syndrome”. Am J Psychiatry 144:25–29

    Google Scholar 

  • Wood PL (1985) Pharmacological evaluation of GABAergic and glutamatergic inputs to the nucleus basalis-cortical and the septal-hippocampal cholinergic projections. Can J Physiol Pharmacol 64:325–328

    Google Scholar 

  • Yang CR, Mogenson GJ (1989) Ventral pallidal neuronal responses to dopamine receptor stimulation in the nucleus accumbens. Brain Res 489:237–246

    Article  PubMed  Google Scholar 

  • Zaborszki L, Heimer L, Eckenstein F, Lernath C (1986) GABAergic input to cholinergic forebrain neurons: an ultrastructural study using retrograde tracing of HRP and double immunolabeling. J Comp Neurol 250:282–295

    Article  PubMed  Google Scholar 

  • Zezula J, Cortex R, Probst A, Palacios JM (1988) Benzodiazepine receptor sites in the human brain: autoradiographic mapping. Neuroscience 25:771–795

    Google Scholar 

  • Zsilla G, Cheney DL, Costa E (1976) Regional changes in the rate of turnover of acetylcholine in rat brain following diazepam or muscimol. Arch Pharmacol 294:251–255

    Article  Google Scholar 

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  1. Department of Psychology, The Ohio State University, 27 Townshend Hall, 43210, Columbus, OH, USA

    M. Sarter, J. P. Bruno & P. Dudchenko

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Sarter, M., Bruno, J.P. & Dudchenko, P. Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. Psychopharmacology 101, 1–17 (1990). https://doi.org/10.1007/BF02253710

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