Abstract
Previous studies of rabbits exposed in utero to cocaine have revealed an increase in the number of neurons which are GABA immunoreactive in the anterior cingulate cortex (ACC), suggesting a cocaine-elicited modification in the balance of excitatory and inhibitory interactions. Of the major calcium binding proteins expressed by different subgroups of GABAergic neurons, parvalbumin has been observed in conditions involving excess excitation, and may serve to protect neurons from excitotoxicity. In the present study, we used immunocy-tochemistry to compare the effects of prenatal cocaine exposure on the postnatal development of parvalbumin immunoreactivity in interneurons of the visual cortex (VC) and ACC. We determined the number and laminar distribution of parvalbumin immunoreactive neurons, and we also assessed the distribution of parvalbumin immunoreactivity within primary, secondary and tertiary dendrites of neurons in these two cortical areas. In both ACC and VC, parvalbumin immunoreactive neurons were first observed around postnatal day 10 (P10) and their number increased rapidly from P10 to P20. At all ages studied (P10 to P60) there was no difference between cocaine-exposed and saline control animals in the number or laminar distribution of parvalbumin immunoreactive neurons in either cortical area. However, the distribution of parvalbumin immunoreactivity within dendrites revealed a significant difference between cocaine-exposed and saline control animals in ACC but not in VC. In ACC, at all ages studied, there was an increase in the number of primary, secondary and tertiary dendrites which were parvalbumin immunoreactive in cocaine-exposed animals compared with saline controls. This difference was most striking in secondary dendrites, and in laminae V and VI. The effect was observed at doses of 4 and 3 mg/kg per injection but not at 2 mg/kg per injection. In contrast to ACC, in VC there was no difference in the number of immunoreactive dendrites in cocaine-exposed animals compared with saline controls. These observations are consistent with the hypothesis that the ACC of rabbits exposed in utero to cocaine is characterized by altered excitatory/inhibitory interactions. ACC receives a dense dopaminergic input, but VC receives minimal dopaminergic innervation. Mechanisms by which the action of cocaine on the developing dopaminergic system may modify the balance of excitation and inhibition in ACC are discussed.
Similar content being viewed by others
References
Aceves J, Floran B, Marinez-Fong D, Benitez J, Sierra A, Flores G (1992) Activation of D1 receptors stimulates accumulation of γ-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats. Neurosci Lett 145: 40–42
Akbari HM, Azmitia EC (1992) Increased tyrosine hydroxylase immunoreactivity in the rat cortex following prenatal cocaine exposure. Exp Brain Res 66: 277–281
Akbari HM, Kramer HK, Whitaker-Azmitia PM, Spear LP, Azmitia EC (1992) Prenatal cocaine exposure disrupts the development of the serotonergic system. Brain Res 572: 57–63
Alcántara S, Ferrer I Soriano E (1993) Postnatal development of parvalbumin and calbindin D28K immunoreactivities in the cerebral cortex of the rat. Anat Embryol 188: 63–73
Bähr S, Wolff JR (1985) Postnatal development of axosomatic synapses in the rat visual cortex: morphogenesis and quantitative evaluation. J Comp Neurol 233 405–420
Baimbridge KG, Celio MR Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15: 303–308
Beauregard M, Ferron A (1991) Dopamine modulates the inhibition induced by GABA in rat cerebral cortex: an iontophoretic study. Eur J Pharmacol 205: 225–231
Benes FM (1993) Relationship of cingulate cortex to schizophrenia and other psychiatric disorders. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 581–605
Benes FM, Sorensen I, Vincent SL, Bird ED, Sathi M (1992) Increased density of glutamate immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cerebral Cortex 2: 503–512
Benes FM, Vincent SL, Molloy R (1993) Dopamine-immunoreactive axon varicosities form nonrandom contacts with GABA-immunoreactive neurons of rat medial prefrontal cortex. Synapse 15: 285–295
Bernath S, Zigmond MJ (1989) Dopamine may influence GABA release via three separate mechanisms. Brain Res 476: 373–376
Best N, Mitchell J, Baimbridge KG, Wheal HV (1993) Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion. Neurosci Lett 155: 1–6
Blaustein MP (1988) Calcium transport and buffering in neurons. Trends Neurosci 11: 438–443
Cameron DL, Williams JT (1993) Dopamine D1 receptors facilitate transmitter release. Nature 366: 344–348
Campbell K, Kaien P, Wictorin K, Lundberg C, Mandel RJ, Bjorklund A (1993) Characterization of GABA release from intrastriatal striatal transplants: dependence on host-derived afferents. Neuroscience 53: 403–415
Celio MR (1986) Parvalbumin in most γ-aminobutyric acid-containing neurons of the rat cerebral cortex. Science 28: 995–997
Cepeda C, Buchwald NA, Levine MS (1993) Neuromodulatory actions of dopamine in the neostriatum are dependent upon excitatory amino-acid receptor subtypes activated. Proc Natl Acad Sci USA 90: 9576–9580
Cepeda C, Radisavljevic Z, Peacock W, Levine MS, Buchwald N (1992) Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex. Synapse 11: 330–341
Chasnoff IJ, Landress HJ, Barret ME (1990) The prevalence of illicit-drug or alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida. N Engl J Med 322: 1202–1206
Chasnoff IJ, Griffith DR, Frier C, Murray J (1992) Cocaine/polydrug use in pregnancy: two-year follow-up. Pediatrics 89: 284–289
Crino PB, Morrison JH, Hof PR (1993) Monoaminergic innervation of cingulate cortex. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 285–312
DeFelipe J (1993) Neocortical neuronal diversity: chemical heterogeneity revealed by colocalization studies of classic neurotransmitters, neuropeptides, calcium-binding proteins, and cell surface molecules. Cerebral Cortex 3: 273–289
Del Rio JA, De Lecea L, Ferrer I, Soriano E (1994) The development of parvalbumin-immunoreactivity in the neocortex of the mouse. Dev Brain Res 81: 247–259
Devinsky O, Luciano D (1993) The contributions of cingulate cortex to human behavior. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 527–556
Devinsky O, Morrell MJ, Vogt BA (1994) Contributions of anterior cingulate cortex to behavior and epilepsy. Brain 1994 118: 279–306
Doering PL, Davidson CL, LaFauce L, Williams CA (1989) Effects of cocaine on the human fetus: a review of clinical studies. DICP 23: 639–645
Dow-Edwards DL, Freed LA, Fico TA (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain. Dev Brain Res 57: 263–268
Du F, Eid T, Lothman EW, Kohler C, Schwarcz R (1995) Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. J Neurosci 15: 6301–6313
Fonseca M, Soriano E, Rerrer I, Martinez A, Tunon T (1993) Chandelier cell axons identified by parvalbumin-immunoreactivity in the normal human temporal cortex and in Alzheimer's disease. Neuroscience 55: 1107–1116
Friedman E, Yadin E, Wang, HY (1996) Effect of prenatal cocaine on dopamine receptor-G protein coupling in mesocortical regions of the rabbit brain. Neuroscience 70: 739–747
Gabriel M (1993) Discriminative avoidance teaming: a model system. In: Vogt BA, Gabriel M (eds) Neurobiology cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 478–526
Goeders N, Bell V, Guidroz A, McNulty M (1990) Dopaminergic involvement in the cocaine-induced up-regulation of benzodiazepine receptors in the rat caudate nucleus. Brain Res 515: 1–8
Gonzales C, Lin RCS, Chesselet MF (1992) Relative sparing of GABAergic interneurons in the striatum of gerbils with ischemia-induced lesions. Neurosci Lett 135: 53–58
Gressens P, Kosofsky BE, Evrard P (1992) Cocaine-induced disturbances of corticogenesis in the developing murine brain. Neurosci Lett 140: 113–116
Grigonis AM, Murphy EH (1994) The effects of epileptic cortical activity on the development of callosal projections. Dev Brain Res 77: 251–255
Gingras JL, Weese-Mayer DE, Hume Jr RF, O'Donnell KJ (1992) Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure. Early Hum Dev 31: 1–24
Harris BT, Charlton ME, Costa E, Grayson DR (1994) Quantitative changes in α1 and α5 γ-aminobutyric acid type A receptor subunit mRNAs and proteins after a single treatment of cerebellar granule neurons with N-methyl-d-aspartate. Mol Pharmacol 45: 637–648
Heizmann CW, Rohrenbeck J, Kamphuis W (1990) Parvalbumin, molecular and functional aspects. Adv Exp Med Biol 269: 57–66
Hendrickson AE, Van Brederode JFM, Mulligan KA, Celio MR (1991) Development of the calcium-binding proteins parvalbumin and calbindin in monkey striate cortex. J Comp Neurol 307: 626–646
Hof PR, Luth HJ, Rogers JH, Celio MR (1993) Calcium-Binding proteins define subpopulations of interneurons in cingulate cortex. In: Vogt BA, Gabriel M (eds) Neurobiology cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 285–312
Hogan D, Berman NEJ (1994) The development of parvalbumin and calbindin-D28K immunoreactive interneurons in kitten visual cortical areas. Dev Brain Res 77: 1–21
Houser CR (1991) GABA neurons in seizure disorders: a review of immunocytochemical studies. Neurochem Res 16: 295–308
Jones L, Fischer I, Levitt P (1996) Non-uniform alteration of dendritic development in the cerebral cortex following prenatal cocaine exposure. Cerebral Cortex 6: 431–445
Kawaguchi Y, Kubota Y (1993) Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28K-immunoreactive neurons in layer V of rat frontal cortex. J Neurophysiol 70: 387–396
Kobayashi K, Emson PC, Mountjoy CQ, Thornton SN, Lawson DEM, Mann DMA (1990) Cerebral cortical calbindin D28K and parvalbumin neurons in Down's syndrome. Neurosci Lett 113: 17–22
Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13: 177–184
Kriegstein AR, Suppes T, Prince DA (1987) Cellular and synaptic physiology and epileptogenesis of developing rat neocortical neurons in vitro. Dev Brain Res 34: 161–171
Lauder JM, Boer GJ, Feenstra MGP, Mirmiran M, Swaab DF, Van Haaren F (eds) (1988) Neurotransmitters as morphogens. Prog Brain Res 73: 365–387
Levitt P, Murphy EH (1994) Events in central nervous system development as the bases for susceptibility to neurotoxicity. In: Chang LN (ed) Principles of neurotoxicity. Dekker, New York
Lewis DA, Lund JS (1990) Heterogeneity of chandelier neurons in monkey neocortex: corticotropin-releasing factorand parvalbumin-immunoreactive populations. J Comp Neurol 293: 599–615
Lidow MS (1994) Effect of prenatal cocaine exposure on the development of the primate cerebral cortex. Soc Neurosci Abstr 20: 596
Lindefors N (1993) Dopaminergic regulation of glutamic acid decarboxylase mRNA expression and GABA release in the striaturn: a review. Prog Neuropsychopharmacol Biol Psychiatry 17: 887–903
Luhmann HJ, Prince DA (1991) Postnatal maturation of the GABAergic system in the rat neocortex. J Neurophsiol 65: 247–263
Mattson MP (1992) Calcium as sculptor and destroyer of neural circuitry. Exp Gerontol 27: 29–49
Mayes LC, Granger RH, Frank MA, Schottenfeld R, Bornstein MH (1993) Neurobehavioral profiles of neonates exposed to cocaine prenatally. Pediatrics 91: 778–783
Meyer JS, Dupont SA (1993) Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity. Brain Res 608: 129–137
Miettinen R, Sirvio J, Riekkinen P Sr, Laakso MP, Riekkinen M, Riekkinen P Jr (1993) Neocortical, hippocampal and septal parvalbuminand somatostatin-containing neurons in young and aged rats: correlation with passive avoidance and water maze performance. Neurosciene 53: 367–378
Miller MW (1986) Maturation of rat visual cortex III. Postnatal morphogenesis and synaptogenesis of local circuit neurons. Dev Brain Res 25: 271–285
Miller MW, Robertson RT (1993) Development of cingulate cortex: Proteins, neurons, and afferents. In: Vogt BA, Gabriel M (eds) Neurobiology cingulate cortex and limbic thalamus. Birkhauser, Boston, pp 151–180
Mione MC, Danevic C, Boardman P, Harris B, Parnavelas JG (1994) Lineage analysis reveals neurotransmitter (GABA or glutamate) but not calcium-binding protein homogeneity in clonally related cortical neurons. J Neurosci 14: 107–123
Morrison JH, Hof PR (1992) The organization of the cerebral cortex: from molecules to circuits. Disc Neurosci 9: 1–7
Murphy EH (1984) Critical periods and the development of the rabbit visual cortex. In: Stone J, Rappaport E (eds) Development of visual pathways in mammals. Alan Liss, New York, pp 439–462
Murphy EH (1995) Effects of cocaine-induced seizures in pregnant rabbits on survival and CNS development of the fetus. Int Soc Dev Psychobiol Abstr
Murphy EH, Magness R (1984) Development of the rabbit visual cortex: a quantitative Golgi analysis. Exp Brain Res 53: 304–314
Murphy EH, Friedman E, Levitt P, Simansky K, Harvey JA (1995a) Responses of pregnant rabbits to repeated cocaine administration: effects on in utero exposed offspring. Soc Neurosci Abstr 21: 708
Murphy EH, Hammer JG, Schumann MD, Groce MY, Wang XH, Jones L (1995b) The rabbit as a model for studies of in utero cocaine exposure. Lab Anim Sci 45: 163–168
Naegele JR, Barnstable CJ (1989) Molecular determinants of GABAergic local-circuit neurons in the visual cortex. Trends Neurosci 12: 28–34
Nitsch C, Sommacal A, Kalt G (1989) GABAergic hippocampal neurons resistant to ischemia-induced neuronal death contain the Ca2+-binding protein parvalbumin. Neurosci Lett 105: 263–268
Nitsch C, Maly IP, Mori D, Scotti AL (1994) Evidence for the colocalization of parvalbumin and glutamate, but not GABA, in the perforant path of the gerbil hippocampal formation: a combined immunocytochemical and microquantitative analysis. J Neurochem 62: 1276–1284
Nitsch C, Scotti AL, Nitsch FM (1995) Distribution of parvalbumin-containing interneurons in the hippocampus of the gerbil: a qualitative and quantitative statistical analysis. J Chem Neuroanat 9: 135–147
Parnavelas JG (1992) Development of GABA-containing neurons in the visual cortex. Prog Brain Res 90: 523–537
Reinoso BS, Undie A, Pimenta A, Levitt P (1993) Dopamine receptor regulation of cerebral regulation of cerebral cortical neurons developing in vitro. Soc Neurosci Abstr 18: 256
Retaux S, Besson MJ, Penit-Soria J (1991) Synergism between D1 and D2 dopamine receptors in the inhibition of the evoked release of [3H]GABA in the rat prefrontal cortex. Neuroscience 43: 323–329
Rodriguez-Sanchez MN, Arilla E (1991) Changes in striatal somatostatin receptors in pups after cocaine administration to pregnant and nursing dams. Neurosci Lett 134: 37–40
Romano AG, Harvey JA (1996) Prenatal exposure to cocaine disrupts discrimination learning in adult rabbits. Pharm Biochem Behav 53: 617–621
Romano AG, Kachelries WJ, Simansky KJ, Harvey JA (1995) Intrauterine exposure to cocaine produces a modality specific acceleration of classical conditioning in adult rabbits. Pharm Biochem Behav 52: 415–420
Ryan L, Ehrlich S, Finnegan L (1987) Cocaine abuse in pregnancy: effects on the fetus and newborn. Neurotoxicol Teratol 9: 295–299
Santiago M, Machado A, Cano J (1993) Regulation of the prefrontal cortical dopamine release by GABAA and GABAB receptor agonists and antagonists. Brain Res 630: 28–31
Simansky KJ, Kachelries WJ (1996) Prenatal exposure to cocaine selectively disrupts motor responding to D-amphetamine in young and mature rabbits. Neuropharmacol (in press)
Sloviter RS (1991) Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the “dormant basket cell” hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus 1: 41–66
Sloviter RS, Sollas AL, Barbara NM, Laxer KD (1991) Calciumbinding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus. J Comp Neurol 308: 381–396
Solbach S, Celio MR (1991) Ontogeny of the calcium binding protein parvalbumin in the rat nervous system. Anat Embryol 184: 103–124
Soriano E, Del Rio JA, Ferrer I, Auladell C, De Lecea L, Alcántara L (1992) Late appearance of parvalbumin-immunoreactive neurons in the rodent cerebral cortex does not follow an “inside-out” sequence. Neurosci Lett 142: 147–150
Spatz WB, Illing RB, Weisenhorn DMV (1994) Distribution of cytochrome oxidase and parvalbumin in the primary visual cortex of the adult and neonate monkey, Callithrix jacchus. J Comp Neurol 339: 519–534
Spear LP, Kirstein CL, Frambes NA (1989) Cocaine effects on the developing central nervous system: behavioral, psychopharma-cological, and neurochemical studies. In: Hutchings DE (ed) Prenatal abuse of licit and illicit drags. Ann NY Acad Sci 562:290–307
Taylor JB, Benes FM (1994) Colocalization of glutamate decarboxylase (GAD), serotonin (5HT) and tyrosine hydroxylase (TH) in rat medial prefrontal cortex (mPFC). Soc Neurosci Abstr 20: 1556
Van Eden CG, Mrzljak L, Voorn P, Uylings HBM (1989) Prenatal development of GABA-ergic neurons in the neocortex of the rat. J Comp Neurol 28: 213–227
Verney C, Alvarez C, Geffard M, Berger B (1990) Ultrastructural double-labelling study of dopamine terminals and GABA-containing neurons in rat anteromedial cerebral cortex. Eur J Neurosci 2: 960–972
Vogt BA, Sikes RW, Swadlow HA, Weyand TG (1986) Rabbit cingulate cortex: cytoarchitecture, physiological border with visual cortex, and afferent cortical connections of visual, motor, postsubicular and intracingulate origin. J Comp Neurol 248: 74–94
Wahlestedt C, Karoum F, Jaskin G, Wyatt RJ, Larhammar D, Ekman R, Reis DJ (1991) Cocaine-induced reduction of brain neuropeptide Y synthesis dependent on medial prefrontal cortex. Proc Natl Acad Sci, USA 88: 2078–2082
Wang XH, Levitt P, Grayson DR, Murphy EH (1995a) Intrauterine cocaine exposure of rabbits: persistent elevation of GABA immunoreactive neurons in anterior cingulate cortex but not visual cortex. Brain Res 689: 32–46
Wang HY, Runyan S, Yadin E, Friedman E (1995b) Prenatal exposure to cocaine selectively reduces D1 dopamine receptor-mediated activation of striatal Gs proteins. J Pharmacol Exp Ther 273: 492–498
Wang HY, Yeung JM, Friedman E (1995c) Prenatal cocaine exposure selectively reduces mesocortical dopamine release. J Pharmacol Exp Ther 273: 1211–1215
Weese-Mayer DE, Klemka-Waiden LM, Chan MK, Gingras JL (1991) Effects of prenatal cocaine exposure on perinatal morbidity and postnatal growth in the rabbit. Dev Pharmol Ther 4: 221–230
Williams SM, Goldman-Rakic PS, Leranth C (1992) The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex. J Comp Neurol 320: 353–369
Wool verton WL, Johnson KM (1992) Neurobiology of cocaine abuse. Trends Pharmacol Sci 13: 193–200
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wang, XH., Jenkins, A.O., Choi, L. et al. Altered neuronal distribution of parvalbumin in anterior cingulate cortex of rabbits exposed in utero to cocaine. Exp Brain Res 112, 359–371 (1996). https://doi.org/10.1007/BF00227942
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00227942