Abstract
The angiotensin converting enzyme (ACE) inhibitors captopril and enalapril and the nootropic piracetam reduced the amnesiogenic effects of cerebral electroshock treatment in mice. These compounds also directly improved passive-avoidance learning if administered before the learning trial. When given immediately after the learning trial, captopril and piracetam were active, but not enalapril. Captopril, but neither enalapril nor piracetam, facilitated memory retrieval after a 2-month retention interval. Unlike those of piracetam, the memory-improving effects of captopril and enalapril are not established by aldosterone-receptor blockade, suggesting that the two types of drug act via different mechanisms of action.
Similar content being viewed by others
References
Arregui A, Lee CM, Emson PC, Iversen LL (1979) Separation of human brain angiotensin-converting enzyme from enkephalin-degrading activity. Eur J Pharmacol 59:141–144
Arregui A, Perry EK, Rossor M, Tomlinson BE (1982) Angiotensin converting enzyme in Alzheimer's disease: Increased activity in caudate nucleus and cortical areas. J Neurochem 38:1490–1492
Benuck M, Marks N (1979) Co-identity of brain angiotensin converting enzyme with a membrane bound peptidyl carboxy-peptidase inactivating met-enkephalin. Biochem Biophys Res Commun 88:215–221
Croog SH, Levine S, Testa MA, Brown B, Bulpitt CJ, Jenkins CD, Klerman GL, Williams GH (1986) The effects of antihypertensive therapy on the quality of life. N Engl J Med 314:1657–1664
Croog SH, Sudilovsky A, Levine S, Testa M (1987) Work performance, absenteeism and antihypertensive medications. J Hypertens [Suppl 1] 5:S47-S54
Deicken RF (1986) Captopril treatment of depression. Biol Psychiatr 21:1425–1428
Erdös EG, Johnson AR, Boyden NT (1978) Hydrolysis of enkephalin by cultured human endothelial cells and by purified peptidyl dipeptidase. Biochem Pharmacol 27:843–848
Etienne P, Zubenko GS (1987) Does captopril elevate mood? TIPS 8:329–330
Frcka G, Lader M (1988) Psychotropic effects of repeated doses of enalapril, propanolol and atenolol in normal subjects. Br J Clin Pharmacol 25:67–73
Igic RP, Gafford JT, Erdos EG (1981) Effect of captopril on proteins and peptide hormones. Biochem Pharmacol 30:683–685
Maran JW, Yates EF (1977) Cortisol secretion during intrapituitary infusion of angiotensin II in conscious dogs. Am J Physiol 233:E273-E285
McGaugh JL, Herz MJ (1972) Memory consolidation. Albion, San Francisco
Mendelsohn FA, Quirion R, Saavedra JM, Aguilera G, Catt KJ (1984) Autoradiographic localization of angiotensin II receptors in rat brain. Proc Natl Acad Sci USA 81:1575–1579
Millar JA, Sturani A, Rubin PC, Lawrie C, Reid JI (1983) Attenuation of the antihypertensive effect of captopril by the opioid receptor antagonist naloxone. Clin Exp Pharmacol Physiol 10:253–259
Mondadori C, Petschke F (1987) Do piracetam-like compounds act centrally via peripheral mechanisms? Brain Res 435:310–314
Mondadori C, Bhatnagar A, Borkowski J, Häusler A (1990) Involvement of a steroidal component in the mechanism of action of piracetam-like nootropics. Brain Res (in press)
Mondadori C, Ducret T, Petschke F (1989) Blockade of the nootropic action of piracetam-like nootropics by adrenalectomy: an effect of dosage? Behav Brain Res 34:155–158
Overton DA (1985) Contextual stimulus effects of drugs and internal states. In: Balsam PD, Tomic AM (eds) Context and learning. Erlbaum Hillsdale, New Jersey, pp 357–384
Overton DA (1978) Major theories of state dependent learning. In: Ho BT, Richards DW, Chute DL (eds) Drug discrimination and state dependent learning. Academic Press New York, pp 263–318
Ramsay DJ, Keil KC, Sharp MC, Shinsako J (1978) Angiotensin II infusion increases vasopressin, ACTH, and 11-hydroxycorticosteroid secretion. Am J Physiol 234:R66-R71
Roth RH (1972) Action of angiotensin on adrenergic nerve endings: enhancement of norepinephrine biosynthesis. Fed Proc 31:1358–1364
Schölkens BA, Xiang Ji-zhou, Unger TH (1983) Central effects of converting enzyme inhibitors. Clin Exp Hypertens [A] 5:1301–1317
Schwartz JC, de la Baume S, Yi CC et al. (1982) Enkephalin metabolism in brain and its inhibition. Prog Neuropsychopharmacol 6:665–671
Stine SM, Yang HYT, Costa E (1980) Inhibition of in situ metabolism of [3H] [met-5]-enkephalin and potentiation of [met-5]-enkephalin analgesia by captopril. Brain Res 188:295–299
Strittmatter SM, Lo MS, Javitch JA, Snyder SH (1984) Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H] captopril: localization to a striatonigral pathway. Proc Natl Acad Sci USA 81:1599–1603
Sudilovsky A, Turnbull BA, Miller LH, Traficante LT (1984) Captopril delays extinction of conditioned avoidance response in the rat. CINP Abstract, 307, Florence
Sudilovsky A, Croop GS, Crook T, Testa M, Levine S, Klerman GL (1986) Differential effects of anti-hypertensive medications on cognitive functioning. ACNP Abstract, 232, Washington DC
Sudilovsky A, Turnbull BA, Miller LH (1986) The effects of zofenopril, captopril, and methyldopa on shuttle avoidance response extinction in rats. CINP Abstract, 284, San Juan
Tukey JW (1977) Exploratory data analysis. Addison-Wesley, London, pp 47ff
Zubenko GS, Nixon RA (1984) Mood-elevation effect of captopril in depressed patients. Am J Psychiatry 141:110–111
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mondadori, C., Etienne, P. Nootropic effects of ACE inhibitors in mice. Psychopharmacology 100, 301–307 (1990). https://doi.org/10.1007/BF02244597
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244597