Abstract
Chronic haloperidol treatment during prenatal and postnatal development was found to induce long-term behavioral and psychopharmacological effects. Rats tested shortly after termination of the chronic treatment at weaning or as young adults were hyperactive in the open field and exhibited an attenuated behavioral response to amphetamine and an accentuated cataleptic response to later doses of haloperidol, when compared with control offspring of the same age. Tests at an intermediate interval (adolescence period) showed no significant difference from control offspring on any of these behavioral measures. Adult rats administered haloperidol chronically for the same duration were also hyperactive after termination of treatment. In contrast to the effects of haloperidol during development, these adults exhibited an accentuated behavioral response to amphetamine and an attenuated cataleptic response to a later dose of haloperidol. Compensatory mechanisms in response to chronic haloperidol treatment during development thus appear to be different from those in adulthood.
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References
Ahlenius S, Engel J, Hoard E, Larsson K, Lundborg P, Sinnerstedt P (1977) Open field behavior and gross motor development in offspring of nursing rat mothers given. Penfluridol. Pharmacol Biochem Behav 6:343–347
Amsel A (1979) The ontogeny of appetitive learning and persistence in the rat. In: Spear NE, Campbell BA (eds) Ontogeny of learning and retention, Lawrence Erlbaum, Hillsdale, New Jersey
Asper H, Baggiolini M, Burki HR, Lauener H, Ruch W, Stille G (1973) Tolerance phenomena with neuroleptics: Catalepsy, apomorphine steretypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. Eur J Pharmacol 22:287–294
Bartolomé J, Seidler FJ, Anderson TR, Slotkin TA (1976) Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system. J Pharmacol Exp Ther 197:293–302
Bauer RH, Duncan DL (1975) Differential effects of d-amphetamine in mature and immature rats. Physiol Behav 3:312–316
Black IA (1974) Growth and development of cholinergic and adrenergic neurons in a sympathetic ganglion: Reciprocal regulation at the synapse. In: Fuxe K, Olson L, Zotterman Y (eds), Dynamics of degeneration and growth in neurons, Pergamon Press, New York
Burt DR, Creese I, Synder SH (1977) Antischizophrenic drugs: Chronic treatment elevates dopamine receptor binding in brain. Science 196:326–327
Carlsson A (1978) Mechanism of action of neuroleptic drugs. In: Lipton MA, DiMascio A, Killam KF (eds), Psychopharmacology: A generation of progress, Raven Press, New York (p. 1057)
Coyle JT, Campochiaro P (1976) Ontogenesis of dopaminergic-cholinergic interactions in the rat striatum: A neurochemical study. J Neurochem 27:673–678
Coyle I, Wayner MJ, Singer G (1976) Behavioral teratogenesis: A critical evaluation. Pharmacol Biochem Behav 5:191–200
Denenberg VH (1977) Assessing the effects of early experience. In: Methods in psychobiology, vol 3, Myers RD (ed), Academic Press, New York, p 127
DiMascio A, Shader RI (eds) (1972) Butyrophenones in psychiatry. Raven Press, New York
Dörner G, Straudt J, Wenzel J, Kvetnansky R, Murgas K (1977) Further evidence of teratogenic effects apparently produced by neurotransmitters during brain differentiation. Endokrinologie 70:326–330
Engel J, Lundborg P (1974) Regional changes in monamine levels and in the rate of tyrosine and tryptophan hydroxylation in 4 week old offspring of nursing mothers treated with the neuroleptic drugs penfluridol. Naunyn Schmiedebergs Arch Pharmacol 282:327–334
Engel J, Ahlenius S, Brown R, Lundborg P (1974) Learning deficits in offspring of the nursing mothers given penfluridol. In: Fuxe K, Olson L, Zotterman Y (eds), Dynamics of degeneration and growth in neurons, Pergamon Press, New York, p 603
File SE, Wardill AG (1975) Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia 44:53–59
Gandelman R (1973) The ontogeny of maternal responsiveness in female Rockland-Swiss albino mice. Horm Behav 4:257–268
Goldberg HL, DiMascio A (1978) Psychotropic drugs in pregnancy. In: Lipton MA, DiMascio A, Killam KR (eds) Psychopharmacology: A generation of progress, Raven Press, New York, p 1047
Guenther WC (1964) Analysis of variance. Prentice-Hall, Englewood Cliffs, N. J.
Himwich WA, Davis JM (1974) Free amino acids in the developing brain as affected by drugs. In: Vernadakis A, Weiner N (eds), Drugs and the developing brain, advances in behavioral biology, vol 8, Plenum Press, New York, p 231
Hughes JA, Sparber SB (1978) D-amphetamine unmasks postnatal consequences of exposure to methylmercury in utero: Methods for studying behavioral teratogenesis. Pharmacol Biochem Behav 8:365–375
Hyttel J (1977) Changes in dopamine synthesis rate in the super-sensitivity phase after treatment with a single dose of neuroleptics. Psychopharmacology 51:205–207
Infurna RN, Spear LP (1979) Developmental changes in amphetamine-induced taste aversions. Pharmacol Biochem Behav 11:31–35
Keppel G (1973) Design and analysis, a researcher's handbook. Prentice-Hall, Englewood Cliffs, N.J.
Lanier LP, Isaacson RL (1977) Early developmental changes in the locomotor response to amphetamine and their relation to hippocampal function. Brain Res 126:567–575
Levi-Montalcini R (1963) Growth and differentiation in the nervous system. In: Allen J (ed) The nature of biological diversity, McGraw Hill, New York, p 261
Lewis PD, Patel AJ, Bendek G, Balzas R (1977) Effect of reserpine on cell proliferation in the developing rat brain: A quantitative histological study. Brain Res 129:299–308
Lundborg P, Ross BE (1974) Increased concentration of homovanillic acid in the brains of infant rabbits after administration of haloperidol to their nursing mothers. J Pharm Pharmacol 26:816–818
Monder H (1978) Effects of prenatal amphetamine on the development of behavior in rats. Dissertation, SUNY at Binghamton, Binghamton, New York
Nomura Y, Segawa T (1978) Apomorphine-induced locomotor stimulation in developing rats treated with 6-hydroxydopa. Eur J Pharmacol 50:152–156
Smythe GA (1977) The role of serotonin and dopamine in hypothalamic-pituitary function. Clin Endocrinol (Oxf.) 7:325–341
Spear LP (1979) The use of psychopharmacological procedures to analyze the ontogeny of learning and retention: Issues and concerns. In: Spear NE, Campbell BA (eds) Ontogeny of learning and retention, Lawrence Erlbaum Associates. Hillsdale, New Jersey, p 135
Thornburg JE, Moore KE (1975) Supersensitivity to dopaminergic agonists induced by haloperidol. National institute on drug abuse research monograph series: Aminergic hypotheses of behavior: Reality or cliche? 3:23–28
Velley L, Blanc G, Tassin JP, Thierry AM, Glowinski J: (1975) Inhibition of striatal dopamine synthesis in rats injected chronically with neuroleptics in their early life. Naunyn Schmiedebergs Arch Pharmacol 288:97–102
Ziv G, Shani J, Givant Y, Buchman O, Sulman FG (1974) Distribution of tritiated haloperidol in lactating and pregnant cows and ewes. Arch Int Pharmacodyn Ther 212:154–163
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Work completed by this author prior to 1977 was published under the name of Linda Patia Lanier
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Spear, L.P., Shalaby, I.A. & Brick, J. Chronic administration of haloperidol during development: Behavioral and psychopharmacological effects. Psychopharmacology 70, 47–58 (1980). https://doi.org/10.1007/BF00432369
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DOI: https://doi.org/10.1007/BF00432369