Skip to main content

The developing cholinergic system as target for environmental toxicants, nicotine and polychlorinated biphenyls (PCBs): Implications for neurotoxicological processes in mice

Neurotoxicity Research volume 3, pages 37–51 (2001)Cite this article

Abstract

During neonatal life, offspring can be affected by toxic agents either by transfer via mother’s milk or by direct exposure. In many mammalian species the perinatal period is characterized by a rapid development of the brain — “the brain growth spurt” (BGS). This period in the development of the mammalian brain is associated with numerous biochemical changes that transform the feto-neonatal brain into that of the mature adult. In rodents, the cholinergic transmitter system undergoes a rapid development during the neonatal period, a time when spontaneous motor behaviour also reaches peak activity. We have observed that low-dose exposure to environmental toxicants such as nicotine, polychlorinated biphenyls (PCBs) and polybrominated diphe-nylethers (PBDE, flame retardants) during the “BGS” can lead to irreversible changes in adult brain function in the mouse. The induction of persistent effects on behaviour and cholinergic nicotinic receptors in the adult animal appears to be limited to a short period during neonatal development. Furthermore, the neurotoxic effects were shown to develop over time, indicating a time-respons/time-dependent effect. This indicates that environmental toxicants, such as nicotine, PCBs and probably PBDEs, might be involved in the slow, implacable induction of neurodegenerative disorders and/or interfere with normal aging processes.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • Ahlbom, J., Fredriksson, A. and Eriksson, P. (1994) Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose-response changes in brain muscarinic receptors and behaviour in neonatal and adult mice. Brain Res.645, 318–324.

    PubMed  Article  CAS  Google Scholar 

  • Ahlbom, J., Fredriksson, A. and Eriksson, P. (1995) Exposure to an organophosphate (DFP) during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice. Brain Res.677, 13–19.

    PubMed  Article  CAS  Google Scholar 

  • Andersson, O. and Blomkvist, G. (1981) Polybrominated aromatic pollutants found in fish in Sweden. Chemosphere10, 1051–1060.

    Article  Google Scholar 

  • Angus, G.R. and Contreras, ML. (1996) Effects of polychlorinated biphenyls on dopamine release from PC12 cells. Toxicol. Lett.89, 191–199.

    PubMed  Article  CAS  Google Scholar 

  • Ankarberg, E., Fredriksson, A. and Eriksson, P. (1998) Interactive effects of PCB and nicotine administered during the neonatal brain development. In “Organohalogen Compounds”,37, 93–96 (Abstract).

    CAS  Google Scholar 

  • Balfour, D.J.K. (1989) Influence of nicotine on the release of monoamines in the brain. In: Nordberg, A., Fuxe, K., Holmstedt, B. and Sundwall, A. (Eds), “Nicotinic receptors in the CNS. Their role in synaptic transmission”. (Elsevier, Prog Brain Res.),79, 165–172.

    Article  CAS  Google Scholar 

  • Bartus, R.T., Dean III, R.L., Beer, B. and Lippa, A.S. (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science217, 408–417.

    PubMed  Article  CAS  Google Scholar 

  • Beani, L., Bianchi, C, Ferraro, L., Nilsson, L., Nordberg, A., Romanelli, L., Spalluto, P., Sundwall, A. and Tanganelli, S. (1989) Effect of nicotine on the release of acetylcholine and amino acids in the brain. In: Nordberg, A., Fuxe, K., Holmstedt, B. and Sundwall, A. (Eds), “Nicotinic Receptors in the CNS. Their role in synaptic transmission” (Elsevier, Prog. Brain Res.),79, 149–155.

    Article  CAS  Google Scholar 

  • Bolles, R.G. and Woods, P.J. (1964) The ontogeny of behaviour in the albino rat. Anim. Behav.12, 427–441.

    Article  Google Scholar 

  • Campbell, B.A., Lytle, L.D. and Fibiger, H.C. (1969) Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science,166, 635–637.

    PubMed  Article  CAS  Google Scholar 

  • Coyle, J.T. and Yamamura, H.I. (1976) Neurochemical aspects of the ontogenesis of cholinergic neurons in the rat brain. Brain Res.118, 429–440.

    PubMed  Article  CAS  Google Scholar 

  • Dahlstrom, A., Lundell, B., Curvall, M. and Thapper, L. (1990) Nicotine and cotinine concentrations in the nursing mother and her infant. Acta Paediatr. Scand.79, 142–147.

    PubMed  Article  CAS  Google Scholar 

  • Davison, A.N. and Dobbing, J. (1968) Applied Neurochemistry, (Blackwell, Oxford) pp. 178–221, 253-316.

    Google Scholar 

  • Dominguez-del-Toro, E., Juiz, T.M., Smillie, F.I., Lindstrom, J. and Criado, M. (1997) Expression of alpha7 neuronal nicotinic receptors during postnatal development of the rat cerebellum. Dev. Brain Res.98, 125–133.

    Article  CAS  Google Scholar 

  • Drachman, D.A. (1977) Cognitive function in man. Does the cholinergic system have a special role? Neurology27, 783–790.

    CAS  Google Scholar 

  • Environmental Health Criteria 162 (1994): Brominated Diphenyl Ethers. World Health Organization, Geneva.

    Google Scholar 

  • Eriksson, P. (1992) Neuroreceptor and behavioural effects of DDT and pyrethroids in immature and adult mammals. In: Isaacson, R.L. and Jensen, K.F. (Eds), “The Vulnerable Brain and Environmental Risks” (Plenum Press, New York), vol. 2, pp. 235–251.

    Google Scholar 

  • Eriksson, P. (1997) Developmental neurotoxicity of environmental agents in the neonate. Neurotoxicology18, 719–726.

    PubMed  CAS  Google Scholar 

  • Eriksson, P. (1998) Perinatal developmental neurotoxicity of PCBs. (Swedish Environmental Protection Agency, Report 4897), pp. 56.

  • Eriksson, P. and Fredriksson, A (1991) Neurotoxic effects of two different pyrethroids, bioallethrin and deltamethrin, on immature and adult mice: Changes in behavioral and muscarinic receptor variables. Toxicol. Appl. Pharmacol.108, 78–85.

    PubMed  Article  CAS  Google Scholar 

  • Eriksson, P. and Fredriksson, A. (1996a) Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse. Environ. Toxicol. Pharmacol.1, 155–165.

    Article  CAS  Google Scholar 

  • Eriksson, P. and Fredriksson, A. (1996b) Neonatal exposure to 2, 2′, 5, 5′-tetrachlorobiphenyl causes increased susceptibility in the cholinergic transmitter system at adult age. Environ. Toxicol. Pharmacol.1, 217–220.

    Article  CAS  Google Scholar 

  • Eriksson, P. and Talts, U. (1999) Neonatal exposure to neurotoxic pesticides increases adult susceptibility: A review of current findings. Neurotoxicology (in press).

  • Eriksson, P., Ahlbom, J. and Fredriksson, A. (1992) Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice. Brain Res.582, 277–281.

    PubMed  Article  CAS  Google Scholar 

  • Eriksson, P., Ankarberg, E. and Fredriksson, A. (2000) Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice. Brain Res.853, 41–48.

    PubMed  Article  CAS  Google Scholar 

  • Falkeborn, Y., Larsson, C, Nordberg, A. and Slanina, P. (1983) A comparison of the regional ontogenesis of nicotine- and muscarine-like binding sites in the mouse brain. Int. J. Dev. Neurochem.1, 187–190.

    Google Scholar 

  • Fein, G.G., Jacobson, J.L., Jacobson, S.W., Schwartz, P.M. and Dowler, J.K. (1984) Prenatal exposure to polychlorinated biphenyls: Effects on birth size and gestational age. J. Pediatr.105, 315–20.

    PubMed  Article  CAS  Google Scholar 

  • Fiedler, E.P., Marks, M.J. and Collins, A.C. (1987) Postnatal development of cholinergic enzymes and receptors in mouse brain. J. Neurochem.,49, 983–990.

    PubMed  Article  CAS  Google Scholar 

  • Finch, C.E. (1994) Biochemistry of aging in the human mammalian brain. In: Siegel, G.J. (Ed), “Basic Neurochemistry: Molecular, Cellular and Medical Aspects”. 5th ed, pp 627-644.

  • Flores, CM., Rogers, S.W., Pabreza, L.A., Wolfe, B.B. and Kellar, K.J. (1992) A subtype of nicotinic cholinergic receptor in rat brain is composed of a cx4 and [32 subunits and is up-regulated by chronic nicotine teatment. Mol. Pharmacol.41, 31–37.

    PubMed  CAS  Google Scholar 

  • Fredriksson, A. (1994) MPTP-induced behavioural deficits in mice: Validity and utility of a model of parkinsonism. Acta Universitatis Upsaliensis, Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine. 486, pp. 48.

  • Fredriksson, A., Fredriksson, M. and Eriksson, P. (1993) Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behaviour in adult mice. Toxicol. Appl. Pharmacol.122, 258–264.

    PubMed  Article  CAS  Google Scholar 

  • Gallenberg, L.A. and Vodicnik, M.J. (1987) Transfer of persistent chemicals in milk. Drug. Metab. Rev.21, 277–317.

    Article  Google Scholar 

  • Greenberg, L.H. and Weiss, B. (1978) p-Adrenergic receptors in aged rat brain: reduced number and capacity of pieal gland to develop supersensitivity. Science201, 61–63.

    PubMed  Article  CAS  Google Scholar 

  • Henningfield, J.E. and Woodson, P.P. (1988) Dose related action of nicotine on behaviour and physiology: review and implication for replacement therapy for nicotine dependence. J. Subst. Abuse.1, 301–317.

    Google Scholar 

  • Hodges, H., Allen, Y., Sinden, J., Lantos, P.L. and Gray, J.A. (1991) Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system -II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery. Neuroscience45, 609–623.

    PubMed  Article  CAS  Google Scholar 

  • Hutzinger, O., Safe, S. and Zitko, V. (1974) The chemistry of PCB’s. (CRC Press, Cleveland).

    Google Scholar 

  • Jacobson, J.L. and Jacobson, S.W. (1996) Intellectual impairment in children exposed to polychlorinated biphenyls in utero. New Engl. J. Med.335, 783–789.

    PubMed  Article  CAS  Google Scholar 

  • Jacobson, J.L., Jacobson, S.W. and Humphrey, H.E.B. (1990) Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive function in young children. J. Pediatr.116, 38–45.

    PubMed  Article  CAS  Google Scholar 

  • James, J.R. and Nordberg, A. (1995) Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: Emphasis on Alzheimer’s disease and Parkinson’s disease Behav. Gen.25, 149–159.

    CAS  Google Scholar 

  • Johansson, U., Fredriksson, A. and Eriksson, P. (1995) Bioal-lethrin causes permanent changes in behavioural and cholinergic muscarinic receptor variables in adult mice exposed neonatally to DDT. Eur. J. Pharmacol.293, 159–166.

    PubMed  Article  CAS  Google Scholar 

  • Karczmar, A.G. (1975) Cholinergic influences on behaviour. In: Waser PG (Ed): “Cholinergic Mechanisms”. (Raven Press, New York), pp. 501–529.

    Google Scholar 

  • Kirk, R.E. (1968) Experimental design; Procedures for Behavioural Sciences. (Brooks / Cole, Belmont, CA).

    Google Scholar 

  • Klasson-Wehler, E., Hovander, L. and Bergman, A. (1997) New organohalogens in human plasma-Identification and quatification. In: “Organohalogen Compounds”33, 420–425 (Abstract).

    Google Scholar 

  • Kolb, B. and Whishaw, I.Q. (1989) Plasticity in the neocortex: mechanisms underlying recovery from early brain damage. Prog. Neurobiol.32, 235–276.

    PubMed  Article  CAS  Google Scholar 

  • Kuhar, M.J., Birdsall, N.J.M., Burgen, A.S.V. and Hulme, E.C. (1980) Ontogeny of muscarinic receptors in rat brain. Brain Res.184, 375–383.

    PubMed  Article  CAS  Google Scholar 

  • Lindner, M.D. and Schallert, T. (1988) Aging and atropine on spatial navigation in the Morris water task. Behav. Neurosci.102, 621–634.

    PubMed  Article  CAS  Google Scholar 

  • Liu, C, Nordberg, A. and Zhang, X. (1996) Differential co-expression of nicotinic acetylcholine receptor a4 and (32 subunit genes in various regions of rat brain. Neuroreport7, 1645–1649.

    PubMed  CAS  Google Scholar 

  • Marks, M.J., Pauly, J.R., Gross, S.D., Deneris, E.S., Hermans-Borgmeyer, I., Heinemann, S.F. and Collins, A.C. (1992) Nicotine binding and nicotinic receptor subunit RNA after chronic nicotine treatment J. Neurosci.12, 2765–2784.

    CAS  Google Scholar 

  • Meironyte, D., Bergman, A. and Noren, K. (1998) Analysis of polybrominated diphenyl ethers in human milk. In: “Organohalogen Compounds”35, 387–390 (Abstract).

    CAS  Google Scholar 

  • Messeri, M.D., Bickmeyer, U., Weinsberg, F. and Wiegand, H. (1997) Congener specific effects by polychlorinated biphenyls on catecholamine content and release in chromaffin cells. Arch. Toxicol.71, 416–421.

    PubMed  Article  CAS  Google Scholar 

  • Messing, R.B., Vasquez, B.J., Spiehler, V.R., Martinez, J.L. Jr. and Jensen, R.A. (1980) 3H-Dihydromorphine binding in brain regions of young and aged rats. Life Sci.26, 921–927.

    PubMed  Article  CAS  Google Scholar 

  • Miao, H., Liu, C, Bishop, K., Gong, Z.H., Nordberg, A. and Zhang, X. (1998) Nicotine exposure during a critical period of development leads to persistent changes in nicotinic acetylcholine receptors of adult rat brain. J. Neurochemistry70, 752–762.

    CAS  Article  Google Scholar 

  • Miner, L.L. and Collins, A.C. (1989) Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. Pharmacol. Biochem. Behav.33, 469–475.

    PubMed  Article  CAS  Google Scholar 

  • Munson, P.J. and Rodbard, D. (1980) Ligand: A versatile computerized approach for characterization of lig-and-binding system. Anal Biochem107, 220–239.

    PubMed  Article  CAS  Google Scholar 

  • Narang, N. (1995) In situ determination of Ml and M2 muscarinic receptor binding sites and mRNAs in young and old rat brain. Mech. Ageing Dev.78, 221–239.

    PubMed  Article  CAS  Google Scholar 

  • Nordberg, A. (1993) Neuronal nicotinic receptors and their implications in ageing and neurodegenerative disorders in mammals. J. Reprod. Fert. Suppl.46, 145–154.

    CAS  Google Scholar 

  • Nordberg, A. and Bergh, C. (1985) Effect of nicotine on passive avoidance behaviour and motoric activity in mice. Acta Pharmacol. Toxicol.56, 337–341.

    CAS  Google Scholar 

  • Nordberg, A., Winblad, B. (1986) Brain nicotinic and muscarinic receptors in normal aging and dementia. In: Fisher A, Hanin I, Lachman C, (Eds.), Alzheimer’s and Parkinson’s - Advances in Behavioural Biology (Plenum Press, New York) pp. 95–108.

    Google Scholar 

  • Nordberg, A., Adem, A., Hardy, J. (1988) Change in nicotinic receptor subtypes in temporal cortex of Alzheimer brains. Neurosci. Lett.86, 317–321.

    PubMed  Article  CAS  Google Scholar 

  • Nordberg, A., Alafuzoff, I. and Winblad, B. (1992) Nicotinic and muscarinic subtypes in the human brain: changes with aging and dementia. J. Neurosci. Res,31, 103–111.

    PubMed  Article  CAS  Google Scholar 

  • Nordberg, A., Zang, X., Fredriksson, A. and Eriksson, P. (1991) Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behaviour in adult mice. Dev. Brain. Res.63, 201–207.

    Article  CAS  Google Scholar 

  • Noren, K. and Meironyte, D. (1998) Contaminants in Swedish human milk. Decreasing levels of organochlorine and increasing levels of organobromine compounds. In “Organohalogen Compounds”38, 1–4 (Abstract).

    CAS  Google Scholar 

  • Orr-Urtreger, A., Goldner, F.M., Saeki, M., Lorenzo, I., Goldberg, L., De-Biasi, M., Dani, J.A., Patrick, J.W. and Beau-det, A.L. (1997) Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotine currents. J. Neuroscince17, 9165–9171.

    CAS  Google Scholar 

  • Overstreet, D.H. and Russel, R.W. (1991) Animal models of memory disorders. In: Boulton, A.A., Baker, G.B., Martin-Iversen, M.T. (Eds), Animal Models in Psychiatry II (Humana Press, Clifton, New Jersey), pp. 315–368.

    Chapter  Google Scholar 

  • Pedigo, Jr. N.M. (1994) Neurotransmitter receptor plasticity in aging. Life Sci.55, 1985–1991.

    PubMed  Article  CAS  Google Scholar 

  • Pilch, H. and Miiller, W.E. (1988) Chronic treatment with cholineor scopolamine indicates the presence of muscarinic cholinergic receptor plasticity in the frontal cortex of young but not of aged mice. J. Neural. Transm.71, 39–43.

    PubMed  Article  CAS  Google Scholar 

  • Rapp, P.R. and Amaral, D.G. (1992) Individual differences in the cognitive and neurobiological consequences of normal aging. TINS15, 340–344.

    PubMed  CAS  Google Scholar 

  • Rodier, P.M. (1980) Chronology of neuron development: Animal studies and their clinical implications. Dev. Med. Child Neurol.22, 525–545.

    PubMed  CAS  Google Scholar 

  • Rodier, P.M., Ingram, J.L., Tisdale, B., Nelson, S., Romano, J. (1996) Embryological origin for autism: Developmental anomalies of the cranial nerve motor nuclei. J. Comp. Neurol.370, 247–261.

    PubMed  Article  CAS  Google Scholar 

  • Rogan, W.J., Gladen, B.C., Hung, K.L., Koong, S.L., Shia, L.Y., Taylor, J.S., Wu, Y.C., Yang, D., Ragan, N.B. and Hsu, C.C. (1988) Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan. Science241, 334–336.

    PubMed  Article  CAS  Google Scholar 

  • Rogers, J.M., Kavlock, R.L. (1996) Developmental toxicology. In: Klassen, CD. (Ed), Casaret and Doull’s Toxicology: The Basic Science of Poisons (McGraw-Hill, New York), pp. 301–331.

    Google Scholar 

  • Samuel, N., Wonnacott, S., Lindstrom, J. and Futerman, A.H. (1997) Parallel increases in [alpha-125I]bungarotoxin binding and alpha 7 nicotinic subunit immunoreactivity during the development of rat hippocampal neurons in culture. Neurosci. Lett.222, 179–182.

    PubMed  Article  CAS  Google Scholar 

  • Seegal, R.F. (1996) Epidemiological and laboratory evidence of PCB-induced neurotoxicity. Crit. Rev. Toxicol.26, 709–737.

    PubMed  Article  CAS  Google Scholar 

  • Seegal, R.F. and Schantz, S.L. (1994) Neurochemical and behavioral sequelae of exposure to dioxins and PCBs. In: Schecter, A. (Ed), “Dioxins and Health” (Plenum Press, New York), pp. 409–447.

    Google Scholar 

  • Seegal, R.F. and Shain, W. (1992) Neurotoxicity of polychlorinated biphenyls. The role of ortho-substituted congeners in altering neurochemical function. In: Isaacson, R.L. and Jensen, K.F. (Eds) “The vulnerable brain and environmental risks” (Plenum Press, New York) vol. 2, pp. 169–195.

    Google Scholar 

  • Seegal, R.F., Bush, B. and Shain, W. (1990) Lightly chlorinated ortho-substituted PCB congeners decrease dopamine in nonhuman primate brain and in tissue culture. Toxicol. Appl. Pharmacol.106, 136–144.

    PubMed  Article  CAS  Google Scholar 

  • Sellstrom, U., Jansson, B., Kierkegaard, A., de Wit, C, Odsjo, T. and Olsson, M. (1993) Plybrominated diphenyl ethers (PBDE) in the biological samples from the Swedish environment. Chemosphere26, 1703–1718.

    Article  Google Scholar 

  • Shain, W., Bush, B. and Seegal, R. (1991) Neurotoxicity of polychlorinated biphenyls: Structure — activity relationship of individual congeners. Toxicol. Appl. Pharmacol.111, 33–42.

    PubMed  Article  CAS  Google Scholar 

  • Shacka, J.J. and Robinson, S.E. (1998) Exposure to prenatal nicotine transiently increases neuronal nicotinic receptor subunit alpha7, alpha4 and beta2 messenger RNAs in the postnatal brain. Neuroscience84, 1151–1161.

    PubMed  Article  CAS  Google Scholar 

  • Sjodin, A., Hagmar, L., Klasson-Wehler, E., Kronholm-Diab, K., Jakobsson, E. and Bergman, A. (1999) Polybrominated diphenyl ethers (PBDEs) in blood from Swedish workers. Environ. Health Crit. (in press).

  • Slotkin, T.A. (1998) Fetal nicotine or cocaine exposure: Which one is worse J. Pharmacol. Exp. Ther.285, 931–945.

    CAS  Google Scholar 

  • Slotkin, T.A., Orband-Miller, L. and Queen, K.L. (1987) Development of [ HJnicotine binding sites in brain. J. Pharmacol. Exp. Ther.233, 361–368.

    Google Scholar 

  • Stanley, J.S., Cramer, P.H., Thornburg, K.R., Remmers, J.C., Breen, J.J. and Schwemberger, J. (1991) Chemosphere23, 1185.

    Article  CAS  Google Scholar 

  • Stitzel, J.A., Robinson, S.F., Marks, M.J. and Collins, A.C. (1997) Differences in the response to nicotine are determined by genetic factors. Adv. Pharmacol. Sci. 279-284.

  • Talts, U., Fredriksson, A. and Eriksson, P. (1998) Changes in behavioural and muscarinic receptor density after neonatal and adult exposure to bioallethrin. Neurobiol. Aging19, 545–552.

    PubMed  Article  CAS  Google Scholar 

  • Tilson, H.A. and Harry, G.J. (1994) Developmental neurotoxicology of polychlorinated biphenyls and related compounds. In: Isaacson, R.L. and Jensen, K.F. (Eds), “The vulnerable brain and environmental risks” (Plenum Press, New York), vol. 3 pp. 267–279.

    Google Scholar 

  • Tilson, H.A., Jacobson, J.L. and Rogan, W.J. (1990) Polychlorinated biphenyls and the developing nervous system: Cross-species comparisons. Neurotox. Teratol.12, 239–248.

    Article  CAS  Google Scholar 

  • Tizabi, Y., Popke, E.J., Rahman, M.A., Nespor, S.M. and Grunberg, N.E. (1997) Hyperactivity induced by prenatal nicotine exposure is associated with an increase in cortical nicotinic receptors. Pharmacol. Biochem. Behav.58, 141–146.

    PubMed  Article  CAS  Google Scholar 

  • Westfall, T.C., Mereu, G., Vickery, L., Perry, H., Naes, L. and Yoon, K.-W.P. (1989) Regulation of nicotine of midbrain dopamine neurons. In: Nordberg, A., Fuxe, K., Holmstedt, B. and Sundwall, A. (Eds), “Nicotinic receptors in the CNS. Their role in synaptic transmission” (Elsevier, Prog Brain Res.),79, 73–185.

    Article  Google Scholar 

  • Whishaw, I.Q. (1985) Cholinergic receptor blockade in the rat impairs locale but not taxon strategies for place navigation in a swimming pool. Behav. Neurosci.99, 979–1005.

    PubMed  Article  CAS  Google Scholar 

  • Whitehouse, P.J. and Au, K.S. (1986) Cholinergic receptors in aging and Alzheimer’s disease. Prog. Neuro-Psychopharmacol. & Biol. Psychiat.10, 665–676.

    Article  CAS  Google Scholar 

  • Whiting, P.J. and Lindstrom, J.M. (1988) Characterization of bovine and human neuronal nicotinic acetylcholine receptors using monoclonal antibodies. J. Neurosci.8, 3395–3404.

    PubMed  CAS  Google Scholar 

  • Winzer-Serhan, U.H. and Leslie, F.M. (1997) Codistribution of nicotine acetylcholine receptor subunit alpha3 and beta4 mRNAs during rat brain development. J. Comp. Neurol.386, 540–554.

    PubMed  Article  CAS  Google Scholar 

  • Wong, D.F., Wagner, H.N., Dannals, R.F., Links, J.M., Frost, J.J., Ravert, H.T., Wilson, A.A., Rosenbaum, A.E., Gjedde, A., Douglass, K.H., Petronis, J.D., Folstein, M.F., Toung, J.K.T., Burns, H.D. and Kuhar, M.J. (1984) Effects of age on dopamine and serotonin receptors measured by position, tomography in the living human brain. Science226, 1393–1396.

    PubMed  Article  CAS  Google Scholar 

  • Wonnacott, S. (1986) a-Bungarotoxin binds to low-affinity nicotine binding sites in rat brain. J. Neurochem.47, 1706–1712.

    PubMed  Article  CAS  Google Scholar 

  • Zhang, X., Wahlstrom, G. and Nordberg, A. (1990) Influence of development and aging on nicotinic receptor subtypes in rodent brain. Int. J. Dev. Neurosci.8, 715–721.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Environmental Toxicology, Uppsala University, Norbyvägen 18 A, S-752 36, Uppsala, Sweden

    Per Eriksson, Emma Ankarberg, Henrik Viberg & Anders Fredriksson

Authors
  1. Per Eriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emma Ankarberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henrik Viberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anders Fredriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Per Eriksson.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Eriksson, P., Ankarberg, E., Viberg, H. et al. The developing cholinergic system as target for environmental toxicants, nicotine and polychlorinated biphenyls (PCBs): Implications for neurotoxicological processes in mice. neurotox res 3, 37–51 (2001). https://doi.org/10.1007/BF03033229

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033229

Keywords

  • Nicotine
  • Nicotinic Receptor
  • Nicotine Exposure
  • Environmental Toxicant
  • nAChR Subunit