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Psychopharmacology

, Volume 78, Issue 2, pp 104–111 | Cite as

Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents

  • R. Cumin
  • E. F. Bandle
  • E. Gamzu
  • W. E. Haefely
Original Investigations

Abstract

The effect of aniracetam (Ro 13-5057, 1-anisoyl-2-pyrrolidinone) was studied on various forms of experimentally impaired cognitive functions (learning and memory) in rodents and produced the following effects: (1) almost complete prevention of the incapacity to learn a discrete escape response in rats exposed to sublethal hypercapnia immediately before the acquisition session; (2) partial (rats) or complete (mice) prevention of the scopolamine-induced short-term amnesia for a passive avoidance task; (3) complete protection against amnesia for a passive avoidance task in rats submitted to electroconvulsive shock immediately after avoidance acquisition; (4) prevention of the long-term retention- or retrieval-deficit for a passive avoidance task induced in rats and mice by chloramphenicol or cycloheximide administered immediately after acquisition; (5) reversal, when administered as late as 1 h before the retention test, of the deficit in retention or retrieval of a passive avoidance task induced by cycloheximide injected 2 days previously; (6) prevention of the deficit in the retrieval of an active avoidance task induced in mice by subconvulsant electroshock or hypercapnia applied immediately before retrieval testing (24 h after acquisition). These improvements or normalizations of impaired cognitive functions were seen at oral aniracetam doses of 10–100 mg/kg. Generally, the dose-response curves were bell-shaped. The mechanisms underlying the activity of aniracetam and its ‘therapeutic window’ are unknown. Piracetam, another pyrrolidinone derivative was used for comparison. It was active only in six of nine tests and had about one-tenth the potency of aniracetam. The results indicate that aniracetam improves cognitive functions which are impaired by different procedure and in different phases of the learning and memory process.

Key words

Aniracetam Piracetam Learning Memory Hypercapnia Scopolamine ECS Cycloheximide Chloramphenicol Rats Mice 

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References

  1. Alpern HP, Marriott JG (1973) Short-term memory: Facilitation and disruption with cholinergic agents. Physiol Behav 11:571–575Google Scholar
  2. Aschwanden W, Kyburz E (1978) European Patent 5143 (F. Hoffmann-La Roche Co)Google Scholar
  3. Barraco RA, Stettner LJ (1976) Antibiotics and memory. Psychol Bull 83:242–302Google Scholar
  4. Bartus RT, Dean RL, Beer B (1980) Memory deficits in aged cebus monkeys and facilitation with central cholinomimetics. Neurobiol Aging 1:145–152Google Scholar
  5. Butler DE, Poschel BPH, Marriott JG (1981) Cognition-activating properties of 3-(aryloxy)pyridines. J Med Chem 24:346–350Google Scholar
  6. Ch'ih JJ, Olszyna DM, Devlin TM (1976) Alteration in plasma and cellular enzyme and protein levels after lethal and nonlethal doses of cycloheximide in the rat. Biochem Pharmacol 25:2407–2408Google Scholar
  7. Ch'ih JJ, Procyk R, Devlin TM (1977) Regulation of mammalian protein synthesis in vivo: Stimulated protein synthesis in liver in vivo after cycloheximide treatment. Biochem J 162:501–507Google Scholar
  8. De Wied D (1979) Neuropeptides and memory. Acta Endocrinol (Suppl) 225:416–418Google Scholar
  9. Flood JF, Rosenzweig MR, Bennett EL, Orme AE (1973) The influence of duration of protein synthesis inhibition on memory. Physiol Behav 10:555–562Google Scholar
  10. Flood JF, Landry DW, Jarvik ME (1981) Cholinergic receptor interactions and their effects on long-term memory processing. Brain Res 215:177–185Google Scholar
  11. Gaitz CM, Varner RV (1979) Pharmacotherapy of age-associated brain syndromes. Interdiscip Top Gerontol 15:169–178Google Scholar
  12. Galzigna L (1980) The possible molecular basis for memory processes in the central nervous system. Mol Aspects Med 3:1–58Google Scholar
  13. Gamzu E, Perrone L (1981) Pharmacological protection against hypoxic and electro brain shock disruption of avoidance retrieval in mice. Fed Proc 7:525Google Scholar
  14. Giurgea C, Mouravieff-Lesuisse F (1971) Effet facilitateur du piracetam sur un apprentissage répétitif. J Pharmacol (Paris) 2:226–227Google Scholar
  15. Giurgea C, Lefevre D, Lescrenier C, David-Remacle M (1971) Pharmacological protection against hypoxia-induced amnesia in rats. Psychopharmacologia 20:160–168Google Scholar
  16. Giurgea C, Mouravieff-Lesuisse F (1972) Effet facilitateur du piracetam sur un apprentissage répétitif chez le rat. J Pharmacol (Paris) 3:17–30Google Scholar
  17. Giurgea C, Salama M (1977) Nootropic drugs. Prog Neuropsychopharmacol 1:235–247Google Scholar
  18. Giurgea C, Greindl MG, Preat S (1978) Pharmacological reactivity of a new memory test in the rat in relation to major and minor tranquilizers. Abstract 11th CINP Congress Vienna, July 9–14, 1978. Vienna Interconvention, p 248Google Scholar
  19. Glick SD, Zimmerberg B (1972) Amnesic effects of scopolamine. Behav Biol 7:245–254Google Scholar
  20. Gold PE, Sternberg DB (1978) Retrograde amnesia produced by several treatments: Evidence for a common neurobiological mechanism. Science 201:367–369Google Scholar
  21. Heise GA (1981) Learning and memory facilitators: Experimental definition and current status. Trends Pharmacol Sci 2:158–160Google Scholar
  22. Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioural effects of nimodipine in animals. Arzneim Forsch 32:347–360Google Scholar
  23. Hunter B, Zornetzer SF, Jarvik ME, McGaugh JL (1977) Modulation of learning and memory: Effects of drugs influencing neurotransmitters. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, vol 8. Plenum, New York, pp 531–577Google Scholar
  24. Izquierdo I, Paiva ACM, Elisabetsky E (1980) Post-training intraperitoneal administration of leu-enkephalin and β-endorphin causes retrograde amnesia for two different tasks in rats. Behav Neural Biol 28:246–250Google Scholar
  25. Jensen TS, De Fine Olivarius B (1980) Transient global amnesia as a manifestation of transient cerebral ischemia. Acta Neurol Scand 61:115–124Google Scholar
  26. Kastin AJ, Coy DH, Schally AV, Miller LH (1978) Peripheral administration of hypothalamic peptides results in CNS changes. Pharmacol Res Commun 10:293–312Google Scholar
  27. Krivanek J, McGaugh JL (1968) Effects of pentylenetetrazol on memory storage in mice. Psychopharmacologia 12:303–321Google Scholar
  28. Lewis DJ (1969) Sources of experimental amnesia. Psychol Rev 76:461–472Google Scholar
  29. Manthei RC, Wright DC, Kenny AD (1973) Altered CSF constituents and retrograde amnesia in rats: A biochemical approach. Physiol Behav 10:517–521Google Scholar
  30. Marlin NA, Berk AM, Miller RR (1979) Vulnerability of memory to electroconvulsive shock in relation to onset and offset of reinforcement. Physiol Behav 22:217–221Google Scholar
  31. Matthies H (1980) Pharmacology of learning and memory. Trends Pharmacol Sci 1:333–336Google Scholar
  32. McGaugh JL, Alpern HP (1966) Effects of electroshock on memory: Amnesia without convulsions. Science 152:665–666Google Scholar
  33. McNamara MC, Miller AT, Benignus VA, Davis JN (1977) Age-related changes in the effect of electroconvulsive shock (ECS) on the in vivo hydroxylation of tyrosine and tryptophan in rat brain. Brain Res 131:313–320Google Scholar
  34. Miller AL, Shamban AT, Corddry DH, Kiney CA (1982) Cerebral metabolic responses to electroconvulsive shock and their modification by hypercapnia. J Neurochem 38:916–924Google Scholar
  35. Nakajima S (1976) Cycloheximide: Mechanisms of its amnesic effect. Curr Dev Psychopharmacol 3:26–53Google Scholar
  36. Nielson HC (1968) Evidence that electroconvulsive shock alters memory retrieval rather than memory consolidation. Exp Neurol 20:3–10Google Scholar
  37. Pfeiffer WD, Bookin HB (1978) Vasopressin antagonizes amnesia in rats following electroconvulsive shock. Pharmacol Biochem Behav 9:261–263Google Scholar
  38. Plum F (1979) Dementia, an approaching epidemic. Nature 279:372–373Google Scholar
  39. Rainbow TC (1978) Role of RNA and protein synthesis in memory formation. Neurochem Res 4:297–312Google Scholar
  40. Reisberg B, Ferris SH, Gershon S (1981) An overview of pharmacologic treatment of cognitive decline in the aged. Am J Psychiatry 138:593–600Google Scholar
  41. Rose SPR (1981) What should a biochemistry of learning and memory be about? Neuroscience 6:811–821Google Scholar
  42. Saletu B, Grünberger J, Linzmayer L (1980) Quantitative EEG and psychometric analyses in assessing CNS activity of Ro 13-5057: A cerebral insufficiency improver. Methods Find Exp Clin Pharmacol 2:269–285Google Scholar
  43. Sara SJ, David-Remacle M (1974) Recovery from electroconvulsive shock-induced amnesia by exposure to the training environment: Pharmacological enhancement by piracetam. Psychopharmacologia 36:59–66Google Scholar
  44. Sara SJ (1980) Memory retrieval deficits: Alleviation by etiracetam, a nootropic drug. Psychopharmacology 68:235–241Google Scholar
  45. Silverman LJ, Metz AS (1973) Numbers of pupils with specific learning disabilities in local public schools in the USA, spring 1970. Ann NY Acad Sci 205:146–157Google Scholar
  46. Squire LR, Davis HP (1981) The pharmacology of memory: A neurobiological perspective. Annu Rev Pharmacol Toxicol 21:323–356Google Scholar
  47. Wender PH, Reimherr FW, Wood DR (1981) Attention deficit disorder (minimal brain dysfunction) in adults. Arch Gen Psychiatry 38:449–456Google Scholar
  48. Wolthuis OL (1971) Experiments with UCB 6215, a drug which enhances acquisition in rats: Its effects compared with those of methamphetamine. Eur J Pharmacol 16:283–297Google Scholar
  49. Wolthuis OL (1981) Behavioral effects of etiracetam in rats. Pharmacol Biochem Behav 15:247–255Google Scholar
  50. Zornetzer SF (1978) Neurotransmitter modulation and memory: A new neuropharmacological phrenology? In: Lipton MA, DiMascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven, New York, pp 637–549Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • R. Cumin
    • 1
  • E. F. Bandle
    • 1
  • E. Gamzu
    • 2
  • W. E. Haefely
    • 1
  1. 1.Pharmaceutical Research Department 1F. Hoffmann-La RocheBaselSwitzerland
  2. 2.Hoffmann-La RocheNutleyUSA

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