Abstract
This work was undertaken in order to assess the organization of the prelimbic area of the medial prefrontal cortex of rats exposed prenatally to cocaine. Pregnant Wistar rats were assigned to the following groups:
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Cocaine—60 mg/kg body wt/d sc, from gestational days 8–22; 0131
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Saline;
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Pair-fed; and
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Nonmanipulated.
Male offspring were perfused on postnatal days 14 and 30. Six brains per group and per age were embedded in celloidin to calculate the volumes of the prelimbic area; sections from the other six brains were embedded in resin and processed for electron microscopy. Using semithin sections (2 μm) of layers II–III and V–VI, the following parameters were calculated:
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The fraction of the neuropil occupied by neurons (VV);
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The packing (NA) density; and
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The numerical (NV) density.
Qualitative alterations consisted of dispersed profiles of degenerated neurons and dendrites in the medial prefrontal cortex. No significant differences were found in the gross morphometric parameters when the cocaine group was compared with the other groups. A high interanimal variation was shown in the prelimbic volumes of postnatal day (PND) 14 cocaine-treated rats, and a decrease in volumes was detected at PND30. Although there are some alterations in the main afferent cortical target area for dopaminergic input, its gross morphometric parameters do not seem to be sufficiently affected to account for the behavioral alterations referred to as being dependent on this brain region.
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References
Akbari H. M. and Azmitia E. C. (1992) Increased tyrosine hydroxylase immunoreactivity in the rat following prenatal cocaine exposure.Dev. Brain Res. 66, 277–281.
Akbari H. M., Kramer H. K., Whitaker-Azmitia P. M., Spear L. P., and Azmitia E. C. (1992) Prenatal cocaine exposure disrupts the development of the serotonergic system.Brain Res. 572, 57–63.
Beck T., Lutz B., Thole U., and Wree A. (1993) Assessing chronic brain damage by quantification of regional volumes in postischemic rat brains.Brain Res. 605, 280–286.
Braendgaard H. and Gundersen H. J. G. (1986) The impact of recent stereological advances on quantitative studies of the nervous system.J. Neurosci. Methods 18, 39–78.
Brutkowski S. (1965) Functions of the prefrontal cortex in animals.Physiol. Rev. 45, 721–746.
Cadete-Leite A., Alves M. C., Tavares M. A., and Paula-Barbosa M. M. (1990) Effects of chronic alcohol intake and withdrawal on the prefrontal neurons and synapses.Alcohol 7, 145–152.
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.
Chen W. J. A., Andersen K. H., and West J. R. (1993) Cocaine exposure during the rat brain growth spurt: studies of neonatal survival, somatic growth and brain development.Neurotoxicol. Teratol. 15, 267–273.
Church M. W., Dintcheff B., and Gessner P. K. (1988) Dose dependent consequences of cocaine on pregnancy outcome in the Long Evans rat.Neurotoxicol. Teratol. 10, 51–58.
Church M. W. and Overbeck G. W. (1990) Prenatal cocaine exposure in the Long Evans rat: II. Dosedependent effects on offspring behavior.Neurotoxicol. Teratol. 12, 335–343.
Church M. W., Overbeck G. W., and Andrzejczak A. L. (1990) Prenatal cocaine exposure in the Long Evans rat: I. Dose-dependent effects on gestation, mortality and postnatal maturation.Neurotoxicol. Teratol. 12, 327–334.
Conover W. J. (1980)Practical Nonparametric Statistics, 2nd ed. Wiley, New York.
Deutch A. Y. and Roth R. H. (1990) The determinants of stress-induced activation of the prefrontal cortical dopamine system.Prog. Brain Res. 85, 357–393.
Dow-Edwards D. L. (1989) Long-term neurochemical and neurobehavioral consequences of cocaine use during pregnancy, inPrenatal Abuse of Licit and Illicit Drugs (Hutchings D. E., ed.),Ann. NY Acad. Sci. 562, 208–289.
Galloway M. P. (1988) Neurochemical interactions of cocaine with dopaminergic systems.TIPS 9, 451–454.
Gingras J. L., Weese-Mayer D. E., Hume R. F. Jr., and O’Donell K. J. (1992) Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.Early Hum. Dev. 31, 1–24.
Glick S. D. and Hinds P. A. (1984) Sex differences in sensitization to cocaine- induced rotation.Eur. J. Pharmacol. 59, 119–121.
Gundersen H. J. G. (1977) Notes on the estimation of the numerical density of arbitrary profiles: the edge effect.J. Microsc. 111, 219–223.
Heyser C. J. and Spear L. P. (1993) A comparison of body weight gain and intake of food and water in pregnant and non-pregnant rats receiving cocaine.Teratology 47, 461.
Heyser C. J., Miller J. S., Spear N. E., and Spear L. P. (1992) Prenatal exposure to cocaine-induced conditioned place preference in the rats.Neurotoxicol. Teratol. 14, 57–64.
Horner C. H., O’Regan M., and Arbuthnott E. (1991) Neural plasticity of the hippocampal (CA1) pyramidal cell—quantitative changes in spine density following handling and injection for drug testing.J. Anat. 174, 229–238.
Johns J. M., Means L. W., Means M. J., and McMillen B. A. (1992) Prenatal exposure to cocaine. I: Effects on gestation, development and activity in Sprague-Dawley rats.Neurotoxicol. Teratol. 14, 337–342.
Karoum F., Suddath R. L., and Wyatt R. J. (1990) Chronic cocaine and rat brain cathecholamines: long-term reduction in hypothalamic and frontal cortex dopamine metabolism.Eur. J. Pharmacol. 186, 1–8.
Madeira M. D., Pereira A., Cadete-Leite A., and Paula-Barbosa M. M. (1990) Estimates of volumes and pyramidal cell numbers in the prelimbic subarea of the prefrontal cortex in experimental hypothyroid rats.J. Anat. 171, 41–56.
Maisonneuve I. M., Keller R. W., and Glick S. D. (1990) Similar effects of d-amphetamine and cocaine on extracellular dopamine levels in medial prefrontal cortex of rats.Brain Res. 535, 221–226.
Meyer J. S. and Dupont S. A. (1993) Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity.Brain Res. 608, 129–137.
Moghaddam B. and Bunney B. J. (1989) Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: comparison to amphetamine.Synapse 4, 156–161.
Neuspiel D. R. and Hamel S. C. (1991) Cocaine and infant behavior—Review article.Dev. Behav. Pediat. 12, 55–64.
Palay S. L. and Chan-Palay V. (1974)Cerebellar Cortex—Cytology and Organization. Springer-Verlag, Berlin.
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 binding associated with an increase in ligand affinity.Pharmacol. Biochem. Behav. 37, 371–373.
Silva-Araújo A., Salgado-Borges J., and Tavares M. A. (1991) Morphological changes in the optic nerve after chronic exposure of neonatal rats to cocaine and amphetamine.Ophthalmic Res. 23, 295–302.
Silva-Araújo A., Salgado-Borges J., Cardoso V., Silva M. C., Castro-Correia J., and Tavares M. A. (1993) Changes in the retinal ganglion cell layer and optic nerve of rats gestationally exposed to cocaine.Exp. Eye Res. 56, 199–206.
Spear L. P., Kirstein C. L., and Frambes N. A. (1989) Cocaine effects on the developing CNS: behavioral, psychopharmacological and neurochemical studies, inPrenatal Abuse of Licit and Illicit Drugs (Hutchings D. E., ed.),Ann. NY Acad. Sci. 562, 290–307.
Sterio D. C. (1984) The unbiased estimation of number and sizes of arbitrary particles using the dissector.J. Microsc. 134, 127–136.
Tavares M. A. and Silva M. C. (1993) Body weight gain and hippocampal volumes of rats exposed neonatally to psychostimulants.Brain Res. 619, 137–145.
Thibault L. (1992) Influence of feeding paradigm in rats on temporal pattern of: II—Brain serotonergic and catecholaminergic systems.Chronobiol. Int. 9, 19–34.
Van Eden C. G., Hoorneman E. D. M., Buijs R. M., Matthijssen M. A. H., Geffard M., and Uylings H. B. M. (1987) Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron microscopical level.Neuroscience 22, 849–862.
Van Eden C. G. and Uylings H. B. M. (1985a) Cytoarchitecture development of the prefrontal cortex in the rat.J. Comp. Neurol. 241, 253–267.
Van Eden C. G. and Yulings H. B. M. (1985b) Postnatal volumetric development of the prefrontal cortex in the rat.J. Comp. Neurol. 241, 268–274.
Venero J. L., Herrera A. J., Machado A., and Cano J. (1992) Changes in neurotransmitter levels associated with the deficiency of some essential amino acids in the diet.Br. J. Nutr. 68, 409–420.
Volpe J. J. (1992) Effect of cocaine use on the fetus.N. Engl. J. Med. 327, 399–407.
Weibel E. R. (1979)Stereological Methods, Practical Methods for Biological Morphometry, vol. 1, Academic, London.
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Xavier, M.R., Tavares, M.A., Machado, J.D. et al. Effects of prenatal cocaine exposure in the prefrontal cortex of the rat. Mol Neurobiol 11, 99–110 (1995). https://doi.org/10.1007/BF02740688
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DOI: https://doi.org/10.1007/BF02740688