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

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.

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References

  1. Alpern HP, Marriott JG (1973) Short-term memory: Facilitation and disruption with cholinergic agents. Physiol Behav 11:571–575

    Google Scholar 

  2. Aschwanden W, Kyburz E (1978) European Patent 5143 (F. Hoffmann-La Roche Co)

  3. Barraco RA, Stettner LJ (1976) Antibiotics and memory. Psychol Bull 83:242–302

    Google Scholar 

  4. Bartus RT, Dean RL, Beer B (1980) Memory deficits in aged cebus monkeys and facilitation with central cholinomimetics. Neurobiol Aging 1:145–152

    Google Scholar 

  5. Butler DE, Poschel BPH, Marriott JG (1981) Cognition-activating properties of 3-(aryloxy)pyridines. J Med Chem 24:346–350

    Google 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 25:2407–2408

    Google 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 162:501–507

    Google Scholar 

  8. De Wied D (1979) Neuropeptides and memory. Acta Endocrinol (Suppl) 225:416–418

    Google Scholar 

  9. Flood JF, Rosenzweig MR, Bennett EL, Orme AE (1973) The influence of duration of protein synthesis inhibition on memory. Physiol Behav 10:555–562

    Google Scholar 

  10. Flood JF, Landry DW, Jarvik ME (1981) Cholinergic receptor interactions and their effects on long-term memory processing. Brain Res 215:177–185

    Google Scholar 

  11. Gaitz CM, Varner RV (1979) Pharmacotherapy of age-associated brain syndromes. Interdiscip Top Gerontol 15:169–178

    Google Scholar 

  12. Galzigna L (1980) The possible molecular basis for memory processes in the central nervous system. Mol Aspects Med 3:1–58

    Google Scholar 

  13. Gamzu E, Perrone L (1981) Pharmacological protection against hypoxic and electro brain shock disruption of avoidance retrieval in mice. Fed Proc 7:525

    Google Scholar 

  14. Giurgea C, Mouravieff-Lesuisse F (1971) Effet facilitateur du piracetam sur un apprentissage répétitif. J Pharmacol (Paris) 2:226–227

    Google Scholar 

  15. Giurgea C, Lefevre D, Lescrenier C, David-Remacle M (1971) Pharmacological protection against hypoxia-induced amnesia in rats. Psychopharmacologia 20:160–168

    Google Scholar 

  16. Giurgea C, Mouravieff-Lesuisse F (1972) Effet facilitateur du piracetam sur un apprentissage répétitif chez le rat. J Pharmacol (Paris) 3:17–30

    Google Scholar 

  17. Giurgea C, Salama M (1977) Nootropic drugs. Prog Neuropsychopharmacol 1:235–247

    Google 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 248

  19. Glick SD, Zimmerberg B (1972) Amnesic effects of scopolamine. Behav Biol 7:245–254

    Google Scholar 

  20. Gold PE, Sternberg DB (1978) Retrograde amnesia produced by several treatments: Evidence for a common neurobiological mechanism. Science 201:367–369

    Google Scholar 

  21. Heise GA (1981) Learning and memory facilitators: Experimental definition and current status. Trends Pharmacol Sci 2:158–160

    Google Scholar 

  22. Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioural effects of nimodipine in animals. Arzneim Forsch 32:347–360

    Google 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 531–577

    Google 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 28:246–250

    Google Scholar 

  25. Jensen TS, De Fine Olivarius B (1980) Transient global amnesia as a manifestation of transient cerebral ischemia. Acta Neurol Scand 61:115–124

    Google Scholar 

  26. Kastin AJ, Coy DH, Schally AV, Miller LH (1978) Peripheral administration of hypothalamic peptides results in CNS changes. Pharmacol Res Commun 10:293–312

    Google Scholar 

  27. Krivanek J, McGaugh JL (1968) Effects of pentylenetetrazol on memory storage in mice. Psychopharmacologia 12:303–321

    Google Scholar 

  28. Lewis DJ (1969) Sources of experimental amnesia. Psychol Rev 76:461–472

    Google Scholar 

  29. Manthei RC, Wright DC, Kenny AD (1973) Altered CSF constituents and retrograde amnesia in rats: A biochemical approach. Physiol Behav 10:517–521

    Google 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 22:217–221

    Google Scholar 

  31. Matthies H (1980) Pharmacology of learning and memory. Trends Pharmacol Sci 1:333–336

    Google Scholar 

  32. McGaugh JL, Alpern HP (1966) Effects of electroshock on memory: Amnesia without convulsions. Science 152:665–666

    Google 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 131:313–320

    Google Scholar 

  34. Miller AL, Shamban AT, Corddry DH, Kiney CA (1982) Cerebral metabolic responses to electroconvulsive shock and their modification by hypercapnia. J Neurochem 38:916–924

    Google Scholar 

  35. Nakajima S (1976) Cycloheximide: Mechanisms of its amnesic effect. Curr Dev Psychopharmacol 3:26–53

    Google Scholar 

  36. Nielson HC (1968) Evidence that electroconvulsive shock alters memory retrieval rather than memory consolidation. Exp Neurol 20:3–10

    Google Scholar 

  37. Pfeiffer WD, Bookin HB (1978) Vasopressin antagonizes amnesia in rats following electroconvulsive shock. Pharmacol Biochem Behav 9:261–263

    Google Scholar 

  38. Plum F (1979) Dementia, an approaching epidemic. Nature 279:372–373

    Google Scholar 

  39. Rainbow TC (1978) Role of RNA and protein synthesis in memory formation. Neurochem Res 4:297–312

    Google Scholar 

  40. Reisberg B, Ferris SH, Gershon S (1981) An overview of pharmacologic treatment of cognitive decline in the aged. Am J Psychiatry 138:593–600

    Google Scholar 

  41. Rose SPR (1981) What should a biochemistry of learning and memory be about? Neuroscience 6:811–821

    Google 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 2:269–285

    Google 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 36:59–66

    Google Scholar 

  44. Sara SJ (1980) Memory retrieval deficits: Alleviation by etiracetam, a nootropic drug. Psychopharmacology 68:235–241

    Google 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 205:146–157

    Google Scholar 

  46. Squire LR, Davis HP (1981) The pharmacology of memory: A neurobiological perspective. Annu Rev Pharmacol Toxicol 21:323–356

    Google Scholar 

  47. Wender PH, Reimherr FW, Wood DR (1981) Attention deficit disorder (minimal brain dysfunction) in adults. Arch Gen Psychiatry 38:449–456

    Google 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 16:283–297

    Google Scholar 

  49. Wolthuis OL (1981) Behavioral effects of etiracetam in rats. Pharmacol Biochem Behav 15:247–255

    Google 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 637–549

    Google Scholar 

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Correspondence to R. Cumin.

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Cumin, R., Bandle, E.F., Gamzu, E. et al. Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Psychopharmacology 78, 104–111 (1982). https://doi.org/10.1007/BF00432244

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Key words

  • Aniracetam
  • Piracetam
  • Learning
  • Memory
  • Hypercapnia
  • Scopolamine
  • ECS
  • Cycloheximide
  • Chloramphenicol
  • Rats
  • Mice