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Abstract:

The neonatal lesion with 6-hydroxydopamine (6-OHDA) in rodents induces juvenile hyperactivity and paradoxical hypolocomotor response to psychostimulants, in striking contrast to what is observed when similar lesions are carried out in adults. The early disruption of central dopaminergic pathways is followed by increased striatal serotonin (5-HT) contents although the functional role of this neurodevelopmental adaptation remains unclear. The aim of the present study is to investigate the participation of this neurochemical imbalance in the main behavioral phenotypes of this model. To this end, mice received a neonatal administration of 6-OHDA that induced an 80% striatal dopamine depletion together with 70% increase in 5-HT. Serotoninergic hyperinnervation was evidenced further by increased [3H] citalopram autoradiographic binding and 5-HT transporter immunohistochemistry in striatal sections. To investigate whether elevated 5-HT was implicated in hyperactivity, we treated control and 6-OHDA neonatally lesioned mice with the selective irreversible tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA) to induce 5-HT depletion. Normalization of striatal 5-HT in 6-OHDA neonatally lesioned mice to control levels reversed hyperactivity to normal locomotor scores, whereas the same extent of 5-HT depletion did not affect spontaneous locomotor activity of control mice. In turn, the paradoxical response to amphetamine in neonatal DA-depleted mice was not prevented by PCPA treatment. Taken together, our results suggest that the increased striatal 5-HT that follows neonatal DA depletion is involved in hyperlocomotor behavior but not in the paradoxical calming response to amphetamine observed in this mouse model. © 2004 Wiley-Liss, Inc.

Registro:

Documento: Artículo
Título:Elevated serotonin is involved in hyperactivity but not in the paradoxical effect of amphetamine in mice neonatally lesioned with 6-hydroxydopamine
Autor:Avale, M.E.; Nemirovsky, S.I.; Raisman-Vozari, R.; Rubinstein, M.
Filiación:Inst. Invest. Ing. Genet./Biol. M., Departamento de Fisiología, Universidad de Buenos Aires, Argentina
INSERM U 289, Hopital de la Salpetriere, Paris, France
Centro de Estudios Cientificos, Valdivia, Chile
INGEBl-CONlCET, Vuelta de Obligado 2490, 1428-Buenos Aires, Argentina
Palabras clave:6-hydroxydopamine; Dopamine; p-chlorophenylalanine; Serotonin; amphetamine; citalopram; fenclonine; oxidopamine; psychostimulant agent; serotonin; serotonin transporter; tritium; tryptophan hydroxylase; animal experiment; animal model; article; autoradiography; controlled study; dopaminergic system; drug effect; female; gene mutation; hyperactivity; male; mouse; nerve cell differentiation; neurotransmission; nonhuman; phenotype; priority journal; serotoninergic system; Amphetamine; Animals; Animals, Newborn; Carrier Proteins; Central Nervous System Stimulants; Corpus Striatum; Dopamine; Dopamine Plasma Membrane Transport Proteins; Fenclonine; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Motor Activity; Nerve Tissue Proteins; Oxidopamine; Serotonin; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
Año:2004
Volumen:78
Número:2
Página de inicio:289
Página de fin:296
DOI: http://dx.doi.org/10.1002/jnr.20245
Título revista:Journal of Neuroscience Research
Título revista abreviado:J. Neurosci. Res.
ISSN:03604012
CODEN:JNRED
CAS:amphetamine, 1200-47-1, 139-10-6, 156-34-3, 2706-50-5, 300-62-9, 51-62-7, 60-13-9, 60-15-1; citalopram, 59729-33-8; fenclonine, 1991-78-2, 7424-00-2; oxidopamine, 1199-18-4, 28094-15-7, 636-00-0; serotonin, 50-67-9; tritium, 10028-17-8; tryptophan hydroxylase, 9037-21-2; Amphetamine, 300-62-9; Carrier Proteins; Central Nervous System Stimulants; Dopamine Plasma Membrane Transport Proteins; Dopamine, 51-61-6; Fenclonine, 7424-00-2; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Oxidopamine, 1199-18-4; Serotonin Plasma Membrane Transport Proteins; Serotonin, 50-67-9; Slc6a4 protein, mouse; Tryptophan Hydroxylase, EC 1.14.16.4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03604012_v78_n2_p289_Avale

Referencias:

  • Archer, T., Danysz, W., Fredriksson, A., Jonsson, G., Luthman, J., Sundstrom, E., Teiling, A., Neonatal 6-hydroxydopamine-induced dopamine depletions: Motor activity and performance in maze learning (1988) Pharmacol Biochem Behav, 31, pp. 357-364
  • Avale, M.E., Falzone, T.L., Gelman, D.M., Low, M.J., Grandy, D.K., Rubinstein, M., The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperaetivity disorder (2004) Mol Psychiatry, 9, pp. 718-726
  • Bishop, C., Tessmer, J.L., Ullrich, T., Rice, K.C., Walker, P.D., Serotonin 5-HT2A receptors underlie increased motor behaviors induced in dopamine-depleted rats by intrastriatal 5-HT2A/2C agonism (2004) J Pharmacol Exp Ther, , in press
  • Björklund, A., Wiklund, L., Descarries, L., Regeneration and plasticity of central serotoninergic neurons: A review (1981) J Physiol (Paris), 77, pp. 247-255
  • Brocco, M., Dekeyne, A., Veiga, S., Girardon, S., Millan, M.J., Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents (2002) Pharmacol Biochem Behav, 71, pp. 667-680
  • Chin, L.G., Ni, D.R., Cheng, F.C., Ho, Y.P., Kuo, J.S., Intrastriatal injection of 5,7-dihydroxytryptamine decreased 5-HT levels in the striatum and suppressed locomotor activity in C57BL/6 mice (1999) Neurochem Res, 24, pp. 719-722
  • Chiavegatto, S., Dawson, V.L., Mamounas, L.A., Koliatsos, V.E., Dawson, T.M., Nelson, R.J., Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase (2001) Proc Natl Acad Sci USA, 98, pp. 1277-1281
  • Cunningham, K.A., Bradberry, C.W., Chang, A.S., Reith, M.E., The role of serotonin in the actions of psychostimulants: Molecular and pharmacological analyses (1996) Behav Brain Res, 73, pp. 93-102
  • Davids, E., Zhang, K., Kula, N.S., Tarazi, F.I., Baldessarini, R.J., Effects of norepinephrine and serotonin transporter inhibitors on hyperactivity induced by neonatal 6-hydroxydopamine lesioning in rats (2002) J Pharmacol Exp Ther, 301, pp. 1097-1102
  • Descarries, L., Soghomonian, J.J., Garcia, S., Doucet, G., Bruno, J.P., Ultrastructural analysis of the serotonin hyperinnervation in adult rat neostriatum following neonatal dopamine denervation with 6-hydroxydopamine (1992) Brain Res, 569, pp. 1-13
  • Deumens, R., Blokland, A., Prickaerts, J., Modeling Parkinson's disease in rats: An evaluation of 6-OHDA lesions of the nigrostriatal pathway (2002) Exp Neurol, 175, pp. 303-317
  • Ferguson, S.A., A review of rodent models of ADHD (2001) Stimulant Drugs and ADHD: Basic and Clinical Neuroscience, pp. 209-220. , Solanto MV, Arnsten AFT, Castellanos FX, editors. New York: Oxford University Press
  • Franklin, K.B.J., Paxinos, G., (2001) The Mouse Brain in Stereotaxic Coordinates, , San Diego, CA: Academic Press
  • Gainetdinov, R.R., Wetsel, W.C., Jones, S.R., Levin, F.D., Jaber, M., Caron, M.G., Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity (1999) Science, 283, pp. 397-401
  • Gately, P.F., Poon, S.L., Segal, D.S., Geyer, M.A., Depletion of brain serotonin by 5,7-dihydroxytryptamine alters the response to amphetamine and the habituation of locomotor activity in rats (1985) Psychopharmcology (Berl), 87, pp. 400-405
  • Gelman, D.M., Noain, D., Avale, M.E., Otero, V., Low, M.J., Rubinstein, M., Transgenic mice engineered to target Cre/loxP-mediated DNA recombination into catecholaminergic neurons (2003) Genesis, 36, pp. 196-202
  • Geyer, M.A., Serotonergic functions in arousal and motor activity (1996) Behav Brain Res, 73, pp. 31-35
  • Heffner, T.G., Seiden, L.S., Possible involvement of serotonergic neurons in the reduction of locomotor hyperactivity caused by amphetamine in neonatal rats depleted of brain dopamine (1982) Brain Res, 244, pp. 81-90
  • Jacobowitz, D.M., Abbot, L.C., (1998) Chemoarchitectonic Atlas of the Developing Mouse Brain, , Boca Raton. FL: CRC Press LLC
  • Jacobs, B.L., Fornal, C.A., Serotonin and motor activity (1997) Curr Opin Neurobiol, 7, pp. 820-825
  • Kent, L., Doerry, U., Hardy, E., Parmar, R., Gingell, K., Hawi, Z., Kirley, A., Craddock, N., Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): Analysis and pooled analysis (2002) Mol Psychiatry, 7, pp. 908-912
  • Kostrzewa, R.M., Reader, T.A., Descarries, L., Serotonin neural adaptations to ontogenetic loss of dopamine neurons in rat brain (1998) J Neurochem, 70, pp. 889-898
  • Luthman, J., Fredriksson, A., Plaznik, A., Archer, T., Ketanserin and mianserin treatment reverses by hyperactivity in neonatally dopamine-lesioned rats (1991) J Psychopharmacol, 5, pp. 418-421
  • Luthman, J., Lindqvist, E., Ogren, S.O., Hyperactivity in neonatally dopamine-lesioned rats requires residual activity in mesolimbic dopamine neurons (1995) Pharmacol Biochem Behav, 51, pp. 159-163
  • Miller, F.E., Heffner, T.G., Kotake, C., Seiden, L.S., Magnitude and duration of hyperactivity following neonatal 6-hydroxydopamine is related to the extent of brain dopamine depletion (1981) Brain Res, 229, pp. 123-132
  • Molina-Holgado, E., Dewar, K.M., Descarries, L., Reader, T.A., Altered dopamine and serotonin metabolism in the dopamine-denervated and serotonin-hyperinnervated neostriatum of adult rat after neonatal 6-hydroxydopamine (1994) J Pharmacol Exp Ther, 270, pp. 713-721
  • Murer, M.G., Dziewczapolski, G., Menalled, L.B., Garcia, M.C., Agid, Y., Gershanik, O., Raisman-Vozari, R., Chronic levodopa is not toxic for remaining dopamine neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions (1998) Ann Neurol, 43, pp. 561-575
  • Oades, R.D., Dopamine may be "hyper" with respect to noradrenaline metabolism, but "hypo" with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder (2002) Behav Brain Res, 130, pp. 97-102
  • Quist, J.F., Barr, C.L., Schachar, R., Roberts, W., Malone, M., Tannock, R., Basile, V.S., Kennedy, J.L., The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder (2003) Mol Psychiatry, 8, pp. 98-102
  • Rothman, R.B., Baumann, M.H., Monoamine transporters and psychostimulant drugs (2003) Eur J Pharmacol, 479, pp. 23-40
  • Sanders-Bush, E., Gallager, D.A., Sulser, F., On the mechanism of brain 5-hydroxytryptamine depletion by p-chloroamphetamine and related drugs and the specificity of their action (1974) Adv Biochem Psychopharmacol, 10, pp. 185-194
  • Shaywitz, B.A., Klopper, J.H., Yager, R.D., Gordon, J.W., Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine (1976) Nature, 261, pp. 153-155
  • Shaywitz, B.A., Yager, R.D., Klopper, J.H., Selective brain dopamine depletion in developing rats: An experimental model of minimal brain dysfunction (1976) Science, 191, pp. 305-308
  • Snyder, A.M., Zigmond, M.J., Lund, R.D., Sprouting of serotoninergic afferents into striatum after dopamine-depleting lesions in infant rats: A retrograde transport and immunocytochemical study (1986) J Comp Neurol, 245, pp. 274-281
  • Takahashi, H., Takada, Y., Nagai, N., Urano, T., Takada, A., Serotonergic neurons projecting to hippocampus activate locomotion (2000) Brain Res, 869, pp. 194-202
  • Zhang, K., Davids, E., Tarazi, F.I., Baldessarini, R.J., Serotonin transporter binding increases in caudate-putamen and nucleus accumbens after neonatal 6-hydroxydopamine lesions in rats: Implications for motor hyperactivity (2002) Brain Res Dev Brain Res, 137, pp. 135-138
  • Zigmond, M.J., Stricker, E.M., Recovery of feeding and drinking by rats after intraventricular 6-hydroxydopamine or lateral hypothalamic lesions (1973) Science, 182, pp. 717-720
  • Zigmond, M.J., Stricker, E.M., Adaptive properties of monoaminergic neurons and their functional implications (1985) Handbook of Neurochemistry, 9, pp. 87-102. , Lajtha A, editor. New York: Plenum Press

Citas:

---------- APA ----------
Avale, M.E., Nemirovsky, S.I., Raisman-Vozari, R. & Rubinstein, M. (2004) . Elevated serotonin is involved in hyperactivity but not in the paradoxical effect of amphetamine in mice neonatally lesioned with 6-hydroxydopamine. Journal of Neuroscience Research, 78(2), 289-296.
http://dx.doi.org/10.1002/jnr.20245
---------- CHICAGO ----------
Avale, M.E., Nemirovsky, S.I., Raisman-Vozari, R., Rubinstein, M. "Elevated serotonin is involved in hyperactivity but not in the paradoxical effect of amphetamine in mice neonatally lesioned with 6-hydroxydopamine" . Journal of Neuroscience Research 78, no. 2 (2004) : 289-296.
http://dx.doi.org/10.1002/jnr.20245
---------- MLA ----------
Avale, M.E., Nemirovsky, S.I., Raisman-Vozari, R., Rubinstein, M. "Elevated serotonin is involved in hyperactivity but not in the paradoxical effect of amphetamine in mice neonatally lesioned with 6-hydroxydopamine" . Journal of Neuroscience Research, vol. 78, no. 2, 2004, pp. 289-296.
http://dx.doi.org/10.1002/jnr.20245
---------- VANCOUVER ----------
Avale, M.E., Nemirovsky, S.I., Raisman-Vozari, R., Rubinstein, M. Elevated serotonin is involved in hyperactivity but not in the paradoxical effect of amphetamine in mice neonatally lesioned with 6-hydroxydopamine. J. Neurosci. Res. 2004;78(2):289-296.
http://dx.doi.org/10.1002/jnr.20245