Abstract
Rats born to mothers treated with propranolol, during days 8–22 of gestation, displayed hyperactivity in the open field which lasted up to 60 days of age and an impairment of avoidance in the shuttle box which was more marked in the male rats. Females exhibited hyperactivity in the open field but developed impaired avoidance learning only when exposed prenatally to both propranolol and hypoxia. Propranolol administration during the last term of pregnancy (days 18–22) affected mostly shuttle box performance. In contrast, hyperactivity could be induced by treatment during various stages of pregnancy, (days 8–22, 8–18, or 18–22) with the duration of hyperactivity being directly related to the length of treatment of the mothers. The possible mechanism of the disruptive effect of propranolol in the fetus and newborn is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aoyagi M, Veshmukh VD, Meyer JS, Kawamura Y, Tagashira Y (1976) Effect of beta adrenergic blockade with propranolol on cerebral blood flow autoregulation and CO2 responsiveness. Stroke 7:291–295
Bartko D (1971) Experimental brain hypoxia, University Park Press, USA
Bertolini A, Poggioli R (1981) Chloramphenicol administration during brain development. Impairment of avoidance learning in adulthood. Science 213:238–239
Blizard DA, Lippman HR, Chen YY (1975) Sex difference in open field behavior in the rat. Physiol Behav 14:601–608
Bonferroni statistics simultaneous statistical inference. In: Miller RG (1966) Probability and statistics. McGraw Hill series 67–70
Bott-Kanner G, Schweitter A, Reisner SH, Joel-Cohen SI, Rosenfeld JB (1980) Propranolol and hydralazine in the management of essential hypertension in pregnancy. Br J Obstet Gynaecol 87:110–114
Brierley JB, Brown AW, Medrum BS (1971) The nature and time course of the neuronal alterations resulting from oligaemia and hypoglycaemia in the brain of Macaca Mulata. Brain Res 25:483–489
Bullock JL, Harris RE, Young R (1975) Treatment of thyrotoxicosis during pregnancy with propranolol. Am J Obstet Gynecol 121:242–245
Campbell BA, Lytle LD, Fibiger HC (1969) Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science 166:635–637
Campbell BA, Mabry PD (1973) The role of catecholamines in the behavioral arousal during ontogenesis. Psychopharmacologia 31:253–264
Carlsson C, Hagerdal M, Kaasik AE, Siesjo B (1977) A catecholamine mediated increase in cerebral oxygen uptake during immobilization stress in rats. Brain Res 119:223–231
Cottrill CM, McAllister RG, Gettes L, Noonan JA (1977) Propranolol therapy during pregnancy, labor and delivery. Evidence for transplancental drug transfer and impaired neonatal drug disposition. J Pediatr 91:812
Daniell HB, Walle Th, Gaffney ThE, Webb JG (1979) Stimulation-induced release of propranolol and norepinephrine from adrenergic neurons. J Pharmacol Exp Ther 208:354–359
Eliahou ME, Silverberg DS, Reisin E, Masshiach S, Romem I (1978) Propranolol in the treatment of hypertension in pregnancy. Br J Obstet Gynaecol 85:431–436
Fiddler G (1975) Propranolol and pregnancy. Lancet 2:722–723
Fitzgerald JD (1969) Perspectives in adrenergic beta receptor blockade. Clin Pharmacol Ther 10:292–306
Gladstone GR, Hordof A, Gersony WM (1975) Propranolol administration during pregnancy. Effect on the fetus. J Pediatr 86:962–964
Griffith AD, Lawrence KM (1974) The effect of hypoxia and hypoglycemia on the brain of the newborn human infant. Dev Med Child Neurol 16:308–319
Habib A, McCarthy J (1977) Effects on the neonate of propranolol administered during pregnancy. J Pediatr 91:808–811
Hedner TH (1978) Central monoamine metabolism and neonatal oxygen deprivation. An experimental study in the rat brain. Acta Physiol Scand Supp 460:1–34
Herrenkohl LR, Politch JA (1978) Effect of prenatal stress on the oestrous cycle of female offspring as adults. Experientia 34:1240–1241
Himms-Hagen J (1967) Sympathetic regulation of metabolism. Pharmacol Rev 19:367–461
Hiroshii W, Ishii SH (1976) The effect of brain ischemia on the levels of cyclic AMP and glycogen metabolism in gerbil brain in vivo. Brain Res 102:385–389
Jennrich R, Sampson P (1977) Analysis of variances and covariances including repeated measures. In Dixon WJ, Brown MB (eds) Biomedical computer programs P-series. University of California Press p 540–580
Jilek L, Fisher J, Krulich L, Tojan S (1964) The reaction of the brain to stagnant hypoxia and anoxia during ontogeny. In Progress in brain res. 9 (The developing brain) p 113–131
Joelson I, Barton MD (1969) The effect of blockade of the beta receptors of the sympathetic nervous system of the fetus. Acta Obstet Gynecol Scand 48:Suppl (3):75–79
Langer A, Hung CHT, McAnulty JA, Harrigan JT, Washington E (1979) Adrenergic blockade, a new approach to hyperthyroidism during pregnancy. Obstet Gynecol 44:181–186
Lessel W, Dietzmann K (1975) Determination of the glycogen contents in the brains of perinatal and newborn rabbits under conditions of experimental hypoxia. Exp Path Biol 10:294–297
Levitan AA, Manion MD (1973) Propranolol therapy during pregnancy and lactation. Am J Cardiol 32:247
Mabry PD, Campbell BA (1973) Serotonergic inhibition of catecholamine induced behavioral arousal. Brain Res 49:381–391
McCullough ML, Blackman DE (1976) The behavioral effects of prenatal hypoxia in the rat. Dev Psychobiol 9:335–342
McKenzie ET, McCulloch J, Harper AM (1976) Influence of endogenous norepinephrine on cerebral blood flow and metabolism. Am J Physiol 231:489–494
McLusky NJ, Naftolin F (1981) Sexual differentiation of the central nervous system. Science 211:1294–1302
Moorcroft WH (1971) Ontogeny of forebrain inhibition of behavioral arousal. Brain Res 35:513–522
Morales-Aquillera A, Vaugham-Williams EM (1965) The effect on cardiac muscle of beta receptor antagonists in relation to their activity as local anesthetics. Br J Pharmacol 24:332–338
Myers RE (1975) Fetal asphyxia due to umbilical cord compression. Biol Neonate 26:21–43
Mylecharane EY, Raper C (1970) Prejunctional actions of some betaadrenoceptor antagonists in the vas deferens of the guinea-pig. Br J Pharmacol 39:128–139
Rosen TS, Lin M, Spector S, Rosen MR (1979) Maternal fetal and neonatal effects of chronic propranolol administration in the rat. J Pharmacol Exp Ther 208:118–122
Savaki HE, Kadekaro M, Ichle J, Sokoloff L (1978) α and β adrenereceptor blockers have opposite effects on energy metabolism of the central auditory system. Nature 276:521–523
Schoenfeld N, Epstein O, Nemesh L, Rosen M, Atsmon A (1978) Effects of propranolol during pregnancy and development of rats. Adverse effects during pregnancy. Pediatr Res 12:747–50
Siesjo BK, Plum F (1971) Cerebral energy metabolism in normoxia and hypoxia. Acta Anesth Scand Suppl XLV 81–101
Szekely JI, Dunai-Kovacs Z, Migleor E, Ronai AZ, Bajusz S (1978) In vivo antagonism by naloxone of morphine, β-endorphin and a synthetic enkephalin analog. J Pharmacol Exp Ther 207:878–883
Towbin A (1971) Organic causes of minimal brain dysfunction: Perinatal origin of minimal cerebral lesions. JAMA 217:1207–1214
Urca G, Nahin RL, Liebeskind JC (1979) Effects of morphine on spontaneous multiple-unit activity: possible relation to mechanisms of analgesia and reward. Exp Neurol 66:248–262
Weisz J, Ward IL (1980) Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring. Endocrinology 106:306–316
Zacest R, Koch-Weser J (1972) Relation of propranolol plasma level to β-blockade during oral therapy. Pharmacology 7:178–184
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Speiser, Z., Shved, A. & Gitter, S. Effect of propranolol treatment in pregnant rats on motor activity and avoidance learning of the offspring. Psychopharmacology 79, 148–154 (1983). https://doi.org/10.1007/BF00427802
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427802