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Attenuation of muscarinic receptor blockade-induced impairment of spatial delayed alternation performance by the triazole MDL 26,479

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Abstract

The interactions between the effects of MDL 26,479 (0.1, 0.39, 1.56, 6.25 mg/kg; IP) and the muscarinic antagonist scopolamine (0.03, 0.1 mg/kg; IP) on the performance of rats in a delayed alternation task (retention intervals: 2, 4, 8, 16, 32 s) were examined. Scopolamine dose-dependently reduced the relative number of correct responses and interacted with the effects of the length of retention intervals. MDL 26,479 did not affect correct responding but attenuated the behavioral impairments produced by scopolamine. Although this task did not explicitly exclude the possibility that the animals acquired mediational response strategies, and although the effects of scopolamine appeared to interfere with the execution of these strategies, to a major extent, the attenuative effects of MDL 26,479 were not related to its effects on mediational strategies. Thus, it is concluded that administration of MDL 26,479 mainly resulted in a re-establishment of the animals' ability to memorize and/or to recall the information required to exert correct responses.

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References

  • 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

    Article  PubMed  Google Scholar 

  • Beleslin DB, Stefanivic-Denic K, Samardzic R (1986) Comparative behavioral effects of anticholinergic agents in cats: psychomotor stimulation and aggression. Pharmacol Biochem Behav 24:581–586

    Article  PubMed  Google Scholar 

  • Bruno JP, Moore H, Dudchenko P, Sarter M (1992) Modulation of frontal cortical acetylcholine release by benzodiazepine receptor ligands: age-dependent effects and behavioral correlates. In: Meyer EM, Crews FT, Simpkins JW (eds) The treatment of dementias: a new generation of progress. Plenum Press, New York

    Google Scholar 

  • Cooper SJ (1985) Bidirectional control of palatable food consumption through a common benzodiazepine receptor: theory and evidence. Brain Res Bull 15:397–410

    Article  PubMed  Google Scholar 

  • Dean RL, Bartus RT (1988) Behavioral models of aging in nonhuman primates. In: Iversen LL, Iversen SD, Snyder SH (eds) Psychopharmacology of the aging nervous system, Handbook of psychopharmacology, vol 20. Plenum Press, New York, pp 325–392

    Google Scholar 

  • Dudchenko P, Sarter M (1991a) GABAergic control of basal forebrain cholinergic neurons and memory. Behav Brain Res 42:33–41

    PubMed  Google Scholar 

  • Dudchenko P, Sarter, M (1991b) Behavioral microanalysis of spatial delayed alternation performance: rehearsal through overt behavior, and effects of scopolamine and chlordiazepoxide. Psychopharmacology 107:263–270

    Google Scholar 

  • Dudley MW, Baron BW, Sorensen SM, Miller FP (1990) MDL 26,479: a potential antidepressant whose mechanism of action involves interaction at the GABAA receptor complex. Am Coll Neuropsychopharmacol, 29th meeting (Abstract)

  • Fibiger HC (1991) Cholinergic mechanisms in learning, memory and dementia: a review of recent evidence. TINS 14:220–223

    PubMed  Google Scholar 

  • Flicker C, Serby M, Ferris SH (1990) Scopolamine effects on memory, language, visuospatial praxis and psychomotor speed. Psychopharmacology 100:243–250

    Google Scholar 

  • Flood JL, Cherkin A (1986) Scopolamine effects on memory retention in mice: a model of dementia? Behav Neural Biol 45:169–184

    Article  PubMed  Google Scholar 

  • Giorgi O, Corda MG, Fernandez A, Biggio G (1989) Theβ-carbolines ZK 93426 and FG 7142 fail to precipitate abstinence signs in diazepam-dependent cats. Pharmacol Biochem Behav 32:671–675

    Article  PubMed  Google Scholar 

  • Grober E, Leipzig RM, Lipton RB, Wisniewski W, Schroeder M, Davies P, Ritter W, Buschke H (1989) Does scopolamine directly impair memory? J Cog Neurosci 1:327–335

    Google Scholar 

  • Hagan J (1992) The status of the cholinergic hypothesis in dementia. In: Nicholson CD (ed) Anti-dementia agents—research and prospects for therapy. Academic Press, New York

    Google Scholar 

  • Heise GA, Hrabrich B, Lilie NL, Martin RA (1975) Scopolamine effects on delayed spatial alternation in the rat. Pharmacol Biochem Behav 3:993–1002

    Article  PubMed  Google Scholar 

  • Inzelberg R, Shapira T, Korczyn AD (1990) Effects of atropine on learning and memory functions in dementia. Clin Neuropharmacol 13:241–247

    PubMed  Google Scholar 

  • Kopelman MD, Corn TH (1988) Cholinergic blockade as a model for cholinergic depletion. Brain 111:1079–1110

    PubMed  Google Scholar 

  • Laties VG (1972) The modification of drug effects on behavior by external discriminative stimuli. J Pharmacol Exp Ther 183:1–13

    PubMed  Google Scholar 

  • Miller JA, Chmielewski PA (1990a) The regulation of high-affinity choline uptake in vitro in rat cortical and hippocampal synaptosomes byβ-carbolines administered in vivo. Neurosci Lett 114:351–355

    Article  PubMed  Google Scholar 

  • Miller JA, Chmielewski PA (1990b) Stimulation of [3]-hermicholinium-3 binding in cortical or hippocampal tissues after treatment withβ-carbolines or MDL 26,479. Soc Neurosci Abstr 16:91.11

    Google Scholar 

  • Miller JA, Dudley M, Kehne JH, Sorensen SM, Kane M (1992) A potential cognition enhancer, MDL, 26,479 increases [3H]hemicholinium-3 binding and long-term potentiation. Brit J Pharmacol (in press)

  • Moerschbaecher JM, Thompson DM, Thomas JR (1979) Effects of methamphetamine and scopolamine on variability of response location. J Exp Anal Behav 32:255–263

    PubMed  Google Scholar 

  • Mueller K, Peel JL (1990) Scopolamine produces locomotor stereotypy in an open field but apomorphine does not. Pharmacol Biochem Behav 36:613–617

    Article  PubMed  Google Scholar 

  • Ngur DO, Rosenberg HC, Chiu TH (1990) Modulation of GABA-stimulated Cl− flux by a benzodiazepine agonist and an “inverse agonist” after chronic flurazepam treatment. Eur J Pharmacol 176:351–356

    Article  PubMed  Google Scholar 

  • Ringo JL (1991) Memory decays at the same rate in macaques with and without brain lesions when expressed in d' or arcsine terms. Behav Brain Res 42:123–134

    PubMed  Google Scholar 

  • Sahgal A (1987) Contrasting effects of vasopressin, desglycinamide-vasopressin and amphetamine on a delayed matching to position task in rats. Psychopharmacology 93:243–249

    Google Scholar 

  • Sarter M (1990) Elevations of local cerebral glucose utilization by the benzodiazepine receptor antagonistβ — carboline ZK 93 426. Eur J Pharmacol 177:155–162

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  • Sarter M, Bruno JP, Dudchenko P (1990) Activating the damaged basal forebrain cholinergic system: tonic stimulation versus signal amplification. Psychopharmacology 101:1–17

    Google Scholar 

  • Sarter M, Bruno JP, Dudchenko P (1991) Cholinergic controversies. TINS 14:484

    PubMed  Google Scholar 

  • Sarter M, Hagan J, Dudchenko P (1992a) Behavioral screening for cognition enhancers: from indiscriminate to valid testing. Part I. Psychopharmacology 107:144–159

    Article  PubMed  Google Scholar 

  • Sarter M, Hagan J, Dudchenko P (1992b) Behavioral screening for cognition enhancers: from indiscriminate to valid testing. Part II. Psychopharmacology 107:461–473

    Article  PubMed  Google Scholar 

  • Shannon HE, Peters SC (1990) A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice. J Pharmacol Exp Ther 255:549–553

    PubMed  Google Scholar 

  • Shannon HE, Bemis KG, Hart JC (1990a) Assessment of working memory in rats using spatial alternation behavior with variable retention intervals: effects of fixed-ratio size and scopolamine. Psychopharmacology 100:491–497

    Google Scholar 

  • Shannon HE, Bemis KG, Hendrix JC, Ward JS (1990b) Interactions between scopolamine and muscarinic agonists or cholinesterase inhibitors on spatial alternation performance in rats. J Pharmacol Exp Ther 255:1071–1077

    PubMed  Google Scholar 

  • Sorensen SM, Miller JA, Moser P, Moran P, Rogers CJ, Dudley M (1990a) MDL 26,479, a novel triazole with potential cognition enhancing activity and a unique profile at the GABAA receptor complex. Am Coll Neuropsychopharmacol, 29th meeting (Abstract)

  • Sorensen SM, Zowlshen JM, Humphreys TM (1990b) An electrophysiological comparison of MDL 26,479, a novel triazole, and beta carbolines in the hippocampal slice: evidence for cognition enhancing potential. Soc Neurosci Abstr 16: 549.16

  • Spencer DG, Jr, Emmett-Oglesby MW (1985) Parallel processing strategies in the application of microcomputers to the behavioral laboratory. Behav Res Methods Instr 17:294–300

    Google Scholar 

  • Sunderland T, Tariot P, Murphy DL, Weingartner H, Mueller EA, Cohen RM (1985) Scopolamine challenges Alzheimer's disease. Psychopharmacology 87:247–249

    Article  PubMed  Google Scholar 

  • Van Hest A, Stroet J, van Haaren F, Feenstra M (1990) Scopolamine differentially disrupts the behavior of male and female wistar rats in a delayed nonmatching to position procedure. Pharmacol Biochem Behav 35:903–909

    Article  PubMed  Google Scholar 

  • White SR (1974) Atropine, scopolamine and hippocampal lesions effects on alternation performance of rats. Pharmacol Biochem Behav 2:297–307

    Article  PubMed  Google Scholar 

  • Zar JH (1974) Biostatistical analysis. Prentice Hall, New Jersey

    Google Scholar 

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Authors and Affiliations

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

    L. A. Holley, P. Dudchenko & M. Sarter

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  1. L. A. Holley
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  2. P. Dudchenko
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  3. M. Sarter
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Holley, L.A., Dudchenko, P. & Sarter, M. Attenuation of muscarinic receptor blockade-induced impairment of spatial delayed alternation performance by the triazole MDL 26,479. Psychopharmacology 109, 223–230 (1992). https://doi.org/10.1007/BF02245504

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  • DOI: https://doi.org/10.1007/BF02245504

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