Skip to main content
SpringerLink
Log in

Prenatal cocaine exposure revealed minimal postnatal changes in rat striatal dopamine D2 receptor sites and mRNA levels in the offspring

  • Proceedings of the Symposium Cellular and Molecular Mechanisms of Drugs of Abuse Cocaine and Methamphetamine held in Nice, France, August 19–20, 1993
  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

It has been reported from this laboratory that prenatal cocaine exposure results in the postnatal transient alterations of rat striatal dopamine uptake sites examined from postnatal 0–32 wk. The present study aims to examine whether this will result in a direct/indirect stimulation of dopamine D2 receptors. Pregnant rats were dosed orally with cocaine hydrochloride (60 mg/kg/d) from gestational day (GD) 7–21. Control animals received an equivalent volume of water. The striatum from the offspring at postnatal 0–32 wk was examined. The radioligand [3H]sulpiride was used for the Scatchard analysis of the D2 receptors, and the changes in the levels of mRNA for the D2 receptor were studied using Northern blot analysis. Results from the present study revealed that in the control group, there was an age-dependent increase in the number of D2 receptor sites (B max:44.00±2.12 to 178.00±45.10 fmol/mg protein) and in the levels of D2 mRNA from PN0–32 wk with the most rapid increase occurring during the first 4 wk of postnatal development. Prenatal cocaine exposure resulted in only a significant decrease (p<0.001) in the number of D2 receptor sites at PN0 wk and in a 10% increase in mRNA levels at PN3, 4, and 12 wk. It was concluded from this study that prenatal cocaine exposure resulted in minimal postnatal changes in the dopamine D2 receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abrams R. M., Burchfield D. J., Gerhardt K. J., and Peters J. M. (1992) Effect of cocaine on electrocortical activity in fetal sheep.Dev. Brain Res. 70, 97–102.

    Article  CAS  Google Scholar 

  • Bilitzke P. J. and Church M. W. (1992) Prenatal cocaine and alcohol exposures affect rat behavior in a stress test (the porsolt swim test).Neurotoxicol. Teratol. 14, 359–364.

    Article  PubMed  CAS  Google Scholar 

  • Bunzow J. R., Van Tol H. H. M., Grandy D. K., Albert P., Salon J., Christie M., Machida C. A., Neve K. A., and Civelli O. (1988) Cloning and expression of a rat D2 dopamine receptor cDNA.Nature 336, 783–787.

    Article  PubMed  CAS  Google Scholar 

  • Burchfield D. J., Graham E. M., Abrams R. M., and Gerhardt K. J. (1990) Cocaine alters behavioral states in fetal sheep.Dev. Brain Res. 56, 41–45.

    Article  CAS  Google Scholar 

  • Carroll F. I., Lewin A. H., Boja J. W., and Kuhar M. J. (1992) Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter.J. Med. Chem. 35, 969–981.

    Article  PubMed  CAS  Google Scholar 

  • Chasnoff I. J., Burns W. J., Schnoll S. H., and Burns K. A. (1985) Cocaine use in pregnancy.N. Engl. J. Med. 313, 666–669.

    Article  PubMed  CAS  Google Scholar 

  • Chasnoff I. J., Burns K. A., Burns W. J., and Schnoll S. H. (1986) Prenatal drug exposure: effects on neonatal and infant growth and development.Neurotoxicol. Teratol. 9, 291–293.

    Article  Google Scholar 

  • Chasnoff I. J., Burns K. A., and Burns W. J. (1987) Cocaine in pregnancy: perinatal morbidity and mortality.Neurobehav. Toxicol. Teratol. 9, 291–293.

    Article  CAS  Google Scholar 

  • Chasnoff I. J., Griffith D. R., MacGregor S., Dirkes K., and Burns K. A. (1989) Temporal patterns of cocaine use in pregnancy.JAMA 261, 1741–1744.

    Article  PubMed  CAS  Google Scholar 

  • Chasnoff I. J., Landress H. J., and Barrett M. E. (1990) The prevalence of illicit-drug or alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, FL.N. Engl. J. Med. 322, 1202–1206.

    Article  PubMed  CAS  Google Scholar 

  • Church M. W. and Overbeck G. W. (1990) Prenatal cocaine exposure in the Long-Evans rat: III. Developmental effects on the brainstem auditory-evoked potential.Neurotoxicol. Teratol. 12, 345–351.

    Article  PubMed  CAS  Google Scholar 

  • Church M. W., Holmes P. A., Overbeck G. W., Tilak J. P., and Zajac C. S. (1991) Interactive effects of prenatal alcohol and cocaine exposures on postnatal mortality, development and behaviour in the Long-Evans rat.Neurotoxicol. Teratol. 13, 377–386.

    Article  PubMed  CAS  Google Scholar 

  • Coles C. D., Platzman K. A., Smith I., James M. E., and Falek A. (1992) Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status.Neurotoxicol. Teratol. 14, 23–33.

    Article  PubMed  CAS  Google Scholar 

  • Corwin M. J., Lester B. M., Sepkoski C., McLaughlin S., Kayne H., and Golub H. L. (1992) Effects of in utero cocaine exposure on newborn acoustical cry characteristics.Pediatrics 89, 1199–1203.

    PubMed  CAS  Google Scholar 

  • Davis M. (1985) Cocaine: excitatory effects on sensorimotor reactivity measured with acoustic startle.Psychopharmacology (Berlin) 86, 31–36.

    Article  CAS  Google Scholar 

  • Dow-Edwards D. L. (1989) Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy.Ann NY Acad. Sci. 562, 280–289.

    Article  PubMed  CAS  Google Scholar 

  • Dow-Edwards D. L., Freed L. A., and Fico T. A. (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain.Dev. Brain Res. 57, 263–268.

    Article  CAS  Google Scholar 

  • Eisen L. N., Field T. M., Bandstra E. S., Roberts J. P., Morrow C., Larson K., and Steele B. M. (1991) Perinatal cocaine effects on neonatal stress behavior and performance on the Brazelton scale.Pediatrics 88, 477–480.

    PubMed  CAS  Google Scholar 

  • Foss J. A. and Riley E. P. (1991) Failure of acute cocaine administration to differentially affect acoustic startle and activity in rats prenatally exposed to cocaine.Neurotoxicol. Teratol. 13, 547–551.

    Article  PubMed  CAS  Google Scholar 

  • Frank D. A., Zuckerman B. S., Amaro H., Aboagye K., Bauchner H., Cabral H., Fried L., Hingson R., Kayne H., Levenson S. M., Parker S., Reece H., and Vinci R. (1988) Cocaine use during pregnancy: prevalence and correlates.Pediatrics 82, 888–895.

    PubMed  CAS  Google Scholar 

  • Freedman S. B., Mustafa A., Poat J., Senior K., Want C., and Woodruff G. N. (1981) A study on the localization of3H-sulpiride binding sites in rat striatal membranes.Neuropharmacology 20, 1151–1155.

    Article  PubMed  CAS  Google Scholar 

  • Freier M. C., Griffith D. R., and Chasnoff I. J. (1991) In utero drug exposure: developmental follow-up and maternal-infant interaction.Sem. Perinatol. 15, 310–316.

    CAS  Google Scholar 

  • Fung Y. K., Reed J. A., and Lau Y. S. (1989) Prenatal cocaine exposure fails to modify neurobehavioral responses and the striatal dopaminergic system in newborn rats.Gen. Pharmacol. 20, 686–693.

    Google Scholar 

  • Gingras J. L., Weese-Mayer D. E., Hume R. F. Jr., and O’Donnell K. J. (1992) Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.Early Hum. Dev. 31, 1–24.

    Article  PubMed  CAS  Google Scholar 

  • Graham W. C., Clarke C. E., Boyce S., Sambrook M. A., Crossman A. R., and Woodruff G. N. (1990) Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intracarotid infusion of MPTP in the monkey (Macaca fascicularis).Brain Res. 514, 103–110.

    Article  PubMed  CAS  Google Scholar 

  • Henderson M. G. and McMillen B. A. (1990) Effects of prenatal exposure to cocaine or related drugs on rat developmental and neurological indices.Brain Res. Bull. 24, 207–212.

    Article  PubMed  CAS  Google Scholar 

  • Henderson M. G., McConnaughey M. M., and McMillen B. A. (1991) Long-term consequences of prenatal exposure to cocaine or related drugs: effects on rat brain monoaminergic receptors.Brain Res. Bull. 26, 941–945.

    Article  PubMed  CAS  Google Scholar 

  • Heyser C. J., Miller J. S., Spear N. E., and Spear L. P. (1992) Prenatal exposure to cocaine disrupts cocaine-dinduced conditioned place preference in rats.Neurotoxicol. Teratol. 14, 57–64.

    Article  PubMed  CAS  Google Scholar 

  • Hutchings D. E., Fico T. A., and Dow-Edwards D. L. (1989) Prenatal cocaine: maternal toxicity, fetal effects and locomotor activity in rat offspring.Neurotoxicol. Teratol. 11, 65–69.

    Article  PubMed  CAS  Google Scholar 

  • Jastrow T. R., Richfield E., and Gnegy M. E. (1984) Quantitative autoradiography of3H-sulpiride binding sits in rat brain.Neurosci. Lett. 51, 47–53.

    Article  PubMed  CAS  Google Scholar 

  • Johns J. M., Means L. W., Means M. J., and McMillen B. A. (1992a) Prenatal exposure to cocaine I: affects on gestation, development, and activity in Sprague-Dawley rats.Neurotoxicol. Teratol. 14, 337–342.

    Article  PubMed  CAS  Google Scholar 

  • Johns J. M., Means M. J., Anderson D. R., Means L. W., and McMillen B. A. (1992b) Prenatal exposure to cocaine II: effects on open-field activity and cognitive behavior in Sprague-Dawley rats.Neurotoxicol. Teratol. 14, 343–349.

    Article  PubMed  CAS  Google Scholar 

  • Joyce J. N., Marshall J. F., Bankiewicz K. S., Kopin I. J., and Jacobwitz D. M. (1986) Hemiparkinsonism in a monkey after unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is associated with regional ipsilateral changes in striatal dopamine D2 receptor density.Brain Res. 382, 360–364.

    Article  PubMed  CAS  Google Scholar 

  • Kuhar M. J., Ritz M. C., and Boja J. W. (1991) The dopamine hypothesis of the reinforcing properties of cocaine.TINS 14, 299–302.

    PubMed  CAS  Google Scholar 

  • Le Moal M. and Simon H. (1991) Mesocorticolimbic dopaminergic netowrk: functional and regulatory roles.Physiol. Rev. 71, 155–234.

    PubMed  Google Scholar 

  • Little B. B., Snell L. M., Palmore M. K., and Gilstrap L. C. III (1988) Cocaine use in pregnant women in a large public hospital.Am. J. Perinatol. 5, 206–207.

    Article  PubMed  CAS  Google Scholar 

  • Lowry O.H., Rosebrough N. J., Farr A. L., and Pandall R. J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.

    PubMed  CAS  Google Scholar 

  • McMillen B. A., Johns J. M., Bass E. W., and Means L. W. (1991) Learning and behaviour of adult rats exposed to cocaine through-out gestation.Teratology 43, 495.

    Google Scholar 

  • Meyer J. S. and Dupont S. A. (1993) Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity.Brain Res. 608, 129–137.

    Article  PubMed  CAS  Google Scholar 

  • Minabe Y., Ashby C. R. Jr., Heyser C., Spear L. P., and Wang R. Y. (1992) The effects of prenatal cocaine exposure on spontaneously active midbrain dopamine neurons in adult male offspring: an electrophysiological study.Brain Res. 586, 152–156.

    Article  PubMed  CAS  Google Scholar 

  • Mofenson H. C. and Caraccio T. R. (1987) Cocaine.Pediatr. Ann. 16, 864–874.

    PubMed  CAS  Google Scholar 

  • Munson P. J. and Rodbard D. (1980) LIGAND: a versatile computerized approach for the characterization of ligand binding systems.Anal. Biochem. 107, 220–239.

    Article  PubMed  CAS  Google Scholar 

  • Neerhof M. G., MacGregor S. N., and Sullivan T. P. (1989) Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome.Am. J. Obstet. Gynecol. 161, 633–638.

    PubMed  CAS  Google Scholar 

  • Neuspiel D. R., Hamel S. C., Hochberg E., Greene J., and Campbell D. (1991) Maternal cocaine use and infant behavior.Neurotoxicol. Teratol. 13, 229–233.

    Article  PubMed  CAS  Google Scholar 

  • Nomura Y., Oki K., and Segawa T. (1982) Ontogenetic development of the striatal [3H]spiperone binding: regulation by sodium and guanine nucleotide in rats.J. Neurochem. 38, 902–908.

    Article  PubMed  CAS  Google Scholar 

  • O’Malley P. M., Bachman J. G., and Johnston L. D. (1988) Period, age, and cohort effects on substance use among young Americans: a decade of change, 1976–1986.Am. J. Public Health 78, 1315–1321.

    PubMed  CAS  Google Scholar 

  • Oro A. S. and Dixon S. D. (1987) Perinatal cocaine and amphetamine exposure: maternal and neonatal correlates.J. Pediatr. 111, 571–578.

    Article  PubMed  CAS  Google Scholar 

  • Peris J. and Zahniser N. R. (1989) Persistent augmented dopamine release after acute cocaine requires dopamine receptor activation.Pharmacol. Biochem. Behav. 32, 71–76.

    Article  PubMed  CAS  Google Scholar 

  • Peris J., Coleman-Hardee M., and Millard W. J. (1992) Cocaine in utero enhances the behavioral response to cocaine in adult rats.Pharmacol. Biochem. Behav. 42, 509–515.

    Article  PubMed  CAS  Google Scholar 

  • Richardson G. A. and Day N. L. (1991) Maternal and neonatal effects of moderate cocaine use during pregnancy.Neurotoxicol. Teratol. 13, 455–460.

    Article  PubMed  CAS  Google Scholar 

  • Riley E. P. and Foss J. A. (1991) Exploratory behavior and locomotor activity: a failure to find effects in animals prenatally exposed to cocaine.Neurotoxicol. Teratol. 13, 553–558.

    Article  PubMed  CAS  Google Scholar 

  • Ritz M. C., Lamb R. J., Goldberg S. R., and Kuhar M. J. (1987) Cocaine receptors on dopamine transporter are related to the self administration of cocaine.J. Pharmacol. Exp. Ther. 248, 1010–1017.

    Google Scholar 

  • Sambrook J. M., Fritsch E. F., and Maniatas T. (1989)Molecular Cloning: A Laboratory Manual, 2nd ed. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.

    Google Scholar 

  • Scalzo F. M., Ali S. F., Frambes N. A., and Spear L. P. (1990) Weanling rats exposed prenatally to cocaine exhibit an increase in striatal D2 dopamine binding associated with an increase in ligand affinity.Pharmacol. Biochem. Behav. 37, 371–373.

    Article  PubMed  CAS  Google Scholar 

  • Schneider J. W., Griffith D. R., and Chasnoff I. J. (1989) Infants exposed to cocaine in utero: implications of developmental assessment and intervention.IYC 2, 25–36.

    Google Scholar 

  • Smith R. F., Mattran K. M., Kurkjian M. F., and Kurtz S. L. (1989) Alterations in offspring behaviour induced by chronic prenatal cocaine dosing.Neurotoxicol. Teratol. 11, 35–38.

    Article  PubMed  CAS  Google Scholar 

  • Sobrian S. K., Burton L. E., Robinson N. L., Ashe W. K., James H., Stokes D. L., and Turner L. M. (1990) Neurobehavioral and immunological effects of prenatal cocaine exposure in rat.Pharmacol. Biochem. Behav. 37, 617–629.

    Article  Google Scholar 

  • Spear L. P., Kirstein C. L., Bell J., Yoottanasumpun V., Greenbaum R., O’Shea J., Hoffman H., and Spear N. E. (1989) Effects of prenatal cocaine exposure on behavior during the early postnatal period.Neurotoxicol. Teratol. 11, 57–63.

    Article  PubMed  CAS  Google Scholar 

  • Stadlin A., Choi H. L., and Tsang D. (1994) Postnatal changes in [3H]mazindol-labelled dopamine uptake sites in the rat striatum following prenatal cocaine exposure.Brain Res. 637, 345–348.

    Article  PubMed  CAS  Google Scholar 

  • Wiggins R. C. (1992) Pharmacokinetics of cocaine in pregnancy and effects on fetal maturation.Clin. Pharmacokinet. 22, 85–93.

    PubMed  CAS  Google Scholar 

  • Zmitrovich A. C., Hutchings D. E., Dow-Edwards D. L., Malowany D., and Church S. (1992) Effects of prenatal exposure to cocaine on the restactivity cycle of the preweanling rat.Pharmacol. Biochem. Behav. 43, 1059–1064.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

    Alfreda Stadlin & Heung Ling Choi

  2. Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

    David Tsang

  3. Department of Biology, The Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong

    Karl Wah Keung Tsim

Authors
  1. Alfreda Stadlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heung Ling Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karl Wah Keung Tsim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stadlin, A., Choi, H.L., Keung Tsim, K.W. et al. Prenatal cocaine exposure revealed minimal postnatal changes in rat striatal dopamine D2 receptor sites and mRNA levels in the offspring. Mol Neurobiol 11, 67–76 (1995). https://doi.org/10.1007/BF02740685

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02740685

Index Entries

Search

Navigation