The interaction between the dopaminergic and the serotonergic systems in the 6-OHDA rat model of Parkinson’s disease

Abstract

This review summarizes published results that are related to the coupling between the dopaminergic and the serotonergic systems and their association to Parkinson’s disease. We focus on the 6-hydroxydopamine rat model of Parkinson’s disease to better understand how dopamine dysfunction affects the serotonergic system, and furthermore to investigate whether a bidi-rectional coupling exists and how it affects functionality and behavior. The accumulated evidence supports a proposed mechanism for this coupling that evolves the lateral habenula.

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Sourani, D. and Goelman, G. (2012) The interaction between the dopaminergic and the serotonergic systems in the 6-OHDA rat model of Parkinson’s disease. Health, 4, 1218-1224. doi: 10.4236/health.2012.431179.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Nilsson, F.M., Kessing, L.V. and Bolwig, T.G. (2001) Increased risk of developing Parkinson’s disease for patients with major affective disorder: A register study. Acta Psychiatrica Scandinavica, 104, 380-386. doi:10.1034/j.1600-0447.2001.00372.x
[2] Schurman, A.G., van den Akker, M., Ensinck, K.T., Metsemakers, J.F., Knottnerus, J.A., Leentjens, A.F. and Buntinx, F. (2002) Increased risk of Parkinson’s disease after depression: A retro-spective cohort study. Neurology, 58, 1501-1504. doi:10.1212/WNL.58.10.1501
[3] Doder, M., Rabiner, E.A., Turjanski, N., Lees, A.J. and Brooks, D.J. (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: An 11C-WAY 100635 PET study. Neurology, 60, 601-605. doi:10.1212/01.WNL.0000031424.51127.2B
[4] Guttman, M., Boileau, I., Warsh, J., Saint-Cyr, J.A., Ginovart, N., McCluskey, T., Houle, S., Wilson, A., Mundo, E., Rusjan, P., Meyer, J. and Kish, S.J. (2007) Brain serotonin transporter binding in non-depressed patients with Parkinson’s disease. European Journal of Neurology, 14, 523-528. doi:10.1111/j.1468-1331.2007.01727.x
[5] Mayeux, R., Stern, Y., Cote, L. and Williams, J.B. (1984) Altered serotonin metab-olism in depressed patients with Parkinson’s disease. Neurology, 34, 642-646. doi:10.1212/WNL.34.5.642
[6] Chen, C.P., et al. (1998) Post-synaptic 5-HT1A and 5- HT2A receptors are increased in Parkinson’s disease neo- cortex. Annals of the New York Academy of Sciences, 861, 288-289. doi:10.1111/j.1749-6632.1998.tb10229.x
[7] Lambert, G., Johansson, M., Agren, H. and Friberg, P. (2000) Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: Evidence in support of the catecholamine hypothesis of mood disorders. Archives of General Psychiatry, 57, 787-793. doi:10.1001/archpsyc.57.8.787
[8] McLean, A., Rubinsztein, J.S., Robbins, T.W. and Sahakian, B.J. (2004) The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression. Psychopharmacology (Berl), 171, 286-297. doi:10.1007/s00213-003-1586-8
[9] D’Haenen, H.A. and Bossuyt, A. (1994) Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biological Psychiatry, 35, 128-132. doi:10.1016/0006-3223(94)91202-5
[10] Chen, J., Paredes, W., Van Praag, H.M., Lowinson, J.H. and Gardner, E.L. (1992) Presynaptic dopamine release is enhanced by 5-HT3 receptor activation in medial prefrontal cortex of freely moving rats. Synapse, 10, 264- 266. doi:10.1002/syn.890100308
[11] El Yacoubi, M., Costentin, J. and Vaugeois, J.M. (2003) Adenosine A2A receptors and depression. Neurology, 61, S82-S87. doi:10.1212/01.WNL.0000095220.87550.F6
[12] Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H. and Del Tredici, K. (2004) Stages in the development of Parkinson’s disease-related pathology. Cell and Tissue Research, 318, 121-134. doi:10.1007/s00441-004-0956-9
[13] Paulus, W. and Jellinger, K. (1991) The neuropathologic basis of different clinical sub-groups of Parkinson’s disease. Journal of Neuropathology & Experimental Neurology, 50, 743-755. doi:10.1097/00005072-199111000-00006
[14] Van Der Kooy, D. and Attori, T. (1980) Dorsal raph′e cells with collateral pro-jections to the caudate-putamen and substantia nigra: A fluo-rescent retrograde double labeling study in the rat. Brain Research, 186, 1-7. doi:10.1016/0006-8993(80)90250-4
[15] Steinbush, H.W.M. (1984) Serotonin-immunoreactive neurons and their projections in the CNS. Handbook of Chemical Neuroanatomy: Classical Transmitter Receptors in the CNS, Part II, Elsevier, Amsterdam, 68-125.
[16] Herv′e, D., Pickel, V.M., Joh, T.H. and Beaudet, A. (1987) Serotonin axon terminals in the ventral tegmental area of the rat: Fine structure and synaptic input to dopaminergic neurons. Brain Research, 435, 71-83. doi:10.1016/0006-8993(87)91588-5
[17] Van Bockstaele, E.J., Biswas, A. and Pickel, V.M. (1993) Topography of serotonin neurons in the dorsal raph′e nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens. Brain Research, 624, 188-198. doi:10.1016/0006-8993(93)90077-Z
[18] Van Bockstaele, E.J., Cestari, D.M. and Pickel, V.M. (1994) Synaptic structure and connectivity of serotonin terminals in the ventral tegmental area: Potential sites for modulation of mesolimbic dopamine neurons. Brain Research, 647, 307-322. doi:10.1016/0006-8993(94)91330-7
[19] Moukhles, H., Bosler, O., Bolam, J.P., Vall ′ee, A., Umbriaco, D., Geffard, M. and Doucet, G. (1997) Quantitative and morphometric data indicate precise cellular interactions between serotonin terminals and postsynaptic targets in rat substantia nigra. Neuroscience, 76, 1159- 1171. doi:10.1016/S0306-4522(96)00452-6
[20] Schwarting, R.K. and Hustonn, J.P. (1996) Unilateral 6-hydroxydopamine lesions of meso-striatal dopamine neurons and their physiological sequelae. Progress in Neuro-biology, 49, 215-266. doi:10.1016/S0301-0082(96)00015-9
[21] Schwarting, R.K. and Huston, J.P. (1996) The unilateral 6-hydroxydopamine lesion model in behavioral brain re- search. Analysis of functional deficits, recovery and treatments. Progress in Neurobi-ology, 50, 275-331. doi:10.1016/S0301-0082(96)00040-8
[22] Deumens, R., Blokland, A. and Prickaerts, J. (2002) Modeling Parkinson’s disease in rats: An evaluation of 6- OHDA lesions of the nigrostriatal pathway. Experimental Neurology, 175, 303-317. doi:10.1006/exnr.2002.7891
[23] Schultz, W. (1982) Depletion of dopamine in the striatum as an experimental model of Parkinsonism: Direct effects and adaptive mechanisms. Progress in Neurobiology, 18, 121-166. doi:10.1016/0301-0082(82)90015-6
[24] Zigmond, M.J., Abercrombie, E.D., Berger, T.W., Grace, A.A. and Stricker, E.M. (1990) Compensations after lesions of central dopaminergic neurons: Some clinical and basic implications. Trends in Neurosciences, 13, 290-296. doi:10.1016/0166-2236(90)90112-N
[25] Forno, L.S. (1969) Concentric hyalin intraneuronal inclusions of Lewy type in the brain of elderly persons (50 incidental cases): Relationship to parkinsonism. Journal of the American Geriatrics Society, 17, 557-575.
[26] Koller, W.C. (1992) When does Parkinson’s disease begin? Neurology, 42, 27-31.
[27] Sawle, G.V. (1993) The detection of preclinical Parkinson’s Disease: What is the role of positron emission tomography? Movement Disorders, 8, 271-277. doi:10.1002/mds.870080304
[28] Rajput, A.H. (1994) Clinical features and natural history of Parkinson’s disease (special consideration of aging). In: Calne, D.P., Ed., Neurodegenerative Diseases, Saunders, Philadelphia, 555-571.
[29] Poewe, W.H. and Wenning, G.K. (1998) The natural history of Parkinson’s disease. Annals of Neurology, 44, 1-9.
[30] Gelb, D.J., Oliver, E. and Gilman, S. (1999) Diagnostic criteria for Parkinson’s disease. Archives of Neurology, 56, 33-39. doi:10.1001/archneur.56.1.33
[31] Wolters, E.C., Francot, C., Bergmans, P., Winogrodzka, A., Booij, J., Berendse, H.W. and Stoof, J.C. (2000) Preclinical (premotor) Parkinson’s disease. Journal of Neurology, 247, 103-109.
[32] Del Tredici, K., Rüb, U., de Vos, R.A.I., Bohl, J.R.E. and Braak, H. (2002) Where does Parkinson disease pathology begin in the brain? Journal of Neuropathology & Experimental Neurology, 61, 413-426.
[33] Braak, H., Del Tredici, K., Rüb, U., de Vos, R.A.I., Jansen Steur, E.N.H. and Braak, E. (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neuro-biology of Aging, 24, 197-211. doi:10.1016/S0197-4580(02)00065-9
[34] Hawkes, C.H., Del Tredici, K. and Braak, H. (2007) Parkinson’s disease: A dual-hit hypothesis. Neuropathology and Applied Neurobiology, 33, 599-614. doi:10.1111/j.1365-2990.2007.00874.x
[35] Cryan, J.F. and Holmes, A. (2005) The ascent of mouse: Advances in modelling human depression and anxiety. Nature Reviews, 4, 775-790. doi:10.1038/nrd1825
[36] Ramos, A., Pereira, E., Martins, G.C., Wehrmeister, T.D. and Izidio, G.S. (2008) Integrating the open field, elevated plus maze and light/dark box to assess different types of emotional behaviors in one single trial. Behavioural Brain Research, 193, 277-288. doi:10.1016/j.bbr.2008.06.007
[37] Lee, C.S., Sauer, H. and Bjorklund, A. (1996) Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat. Neuroscience, 72, 641-653. doi:10.1016/0306-4522(95)00571-4
[38] Tadaiesky, M.T., et al. (2008) Emotional, cognitive and neurochemical alterations in a premotor stage model of Parkinson’s disease. Neuroscience, 156, 830-840. doi:10.1016/j.neuroscience.2008.08.035
[39] Branchi, I., et al. (2008) Nonmotor symptoms in Parkinson’s disease: Investigating early-phase onset of behavioral dysfunction in the 6-hydroxydopamine-lesioned rat model. Journal of Neurosci-ence Research, 86, 2050-2061. doi:10.1002/jnr.21642
[40] Sourani, D., Eitan, R., Gordon, N. and Goelman, G. (2012) The habenula couples the dopaminergic and the serotonergic systems: Application to depression in Parkinson’s disease. European Journal of Neuroscience, 36, 2822- 2829. doi:10.1111/j.1460-9568.2012.08200.x
[41] Winter, C., von Rumohr, A., Mundt, A., Petrus, D., Klein, J., Lee, T., Morgen-stern, R., Kupsch, A. and Juckel, G. (2007) Lesions of dopa-minergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats. Behavioral Brain Research, 184, 133-141. doi:10.1016/j.bbr.2007.07.002
[42] Santiago, R.M., Barbieiro, J., Lima, M.M., Dombrowski, P.A., Andreatini, R. and Vital, M.A. (2010) Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson’s Disease are predominantly associated with serotonin and dopamine. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 34, 1104-1114. doi:10.1016/j.pnpbp.2010.06.004
[43] Wang, S., et al. (2009) Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal firing of the midbrain raphe nuclei 5-HT neurons and a decrease of their response to 5-HT(1A) receptor stimulation in the rat. Neuroscience, 159, 850-861. doi:10.1016/j.neuroscience.2008.12.051
[44] Kaya, A.H., et al. (2008) Increased electrical and metabolic activity in the dorsal raphe nucleus of Parkinsonian rats. Brain Research, 1221, 93-97. doi:10.1016/j.brainres.2008.05.019
[45] Temel, Y., et al. (2007) Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-fre- quency stimulation of the subthalamic nucleus. Proceedings of the National Academy of Sciences of the United States of America, 104, 17087-17092. doi:10.1073/pnas.0704144104
[46] Pelled, G., Bergman, H., Ben-Hur, T. and Goelman, G. (2007) Manganese-enhanced MRI in a rat model of Parkinson’s disease. Journal of Magnetic Resonance Imaging, 26, 863-870. doi:10.1002/jmri.21051
[47] Pautler, R.G., Silva, A.C. and Koretsky, A.P. (1998) In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging. Magnetic Resonance in Medicine, 40, 740-748. doi:10.1002/mrm.1910400515
[48] Koretsky, A.P. and Silva, A.C. (2004) Manganese-enhanced magnetic resonance imaging (MEMRI). NMR in Biomedicine, 17, 529-539. doi:10.1002/nbm.940
[49] Saleem, K.S., et al. (2002) Magnetic resonance imaging of neuronal connections in the macaque monkey. Neuron, 34, 685-700. doi:10.1016/S0896-6273(02)00718-3
[50] Herkenham, M. and Nauta, W.J. (1977) Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem. The Journal of Comparative Neurology, 173, 123-146. doi:10.1002/cne.901730107
[51] Geisler, S. and Trimble, M. (2008) The lateral habenula: No longer neglected. CNS Spectrums, 13, 484-489.
[52] Araki, M., McGeer, P.L. and Kimura, H. (1988) The efferent projections of the rat lateral habenular nucleus revealed by the PHA-L anterograde tracing method. Brain Research, 441, 319-330. doi:10.1016/0006-8993(88)91410-2
[53] Sartorius, A. and Henn, F.A. (2007) Deep brain stimulation of the lateral habenula in treatment resistant major depression. Medical Hypotheses, 69, 1305-1308. doi:10.1016/j.mehy.2007.03.021
[54] Sartorius, A., et al. (2010) Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biological Psychiatry, 67, e9- e11. doi:10.1016/j.biopsych.2009.08.027
[55] Morris, J.S., Smith, K.A., Cowen, P.J., Friston, K.J. and Dolan, R.J. (1999) Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion. Neuroimage, 10, 163-172. doi:10.1006/nimg.1999.0455
[56] Smith, K.A., Morris, J.S., Friston, K.J., Cowen, P.J. and Dolan, R.J. (1999) Brain mechanisms associated with depressive relapse and associated cognitive impairment following acute tryptophan depletion. The British Journal of Psychiatry, 174, 525-529. doi:10.1192/bjp.174.6.525
[57] Caldecott-Hazard, S., Mazziotta, J. and Phelps, M. (1988) Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography. The Journal of Neuroscience, 8, 1951-1961.
[58] Shumake, J., Edwards, E. and Gonzalez-Lima, F. (2003) Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior. Brain Research, 963, 274-281. doi:10.1016/S0006-8993(02)04048-9
[59] Matsumoto, M. and Hikosaka, O. (2007) Lateral habenula as a source of negative reward signals in dopamine neurons. Nature, 447, 1111-1115. doi:10.1038/nature05860
[60] Ferraro, G., Montalbano, M.E., Sardo, P. and La Grutta, V. (1997) Lateral habenula and hippocampus: a complex interaction raphe cells-mediated. Journal of Neural Transmission, 104, 615-631. doi:10.1007/BF01291880
[61] Li, A., et al., (2006) Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons. FASEB Journal, 20, 1263-1265. doi:10.1096/fj.05-5510fje
[62] Tien, L.T., et al. (2003) Increased dopamine D2 receptor binding and enhanced apomorphine-induced locomotor activity in mu-opioid receptor knockout mice. Brain Research Bulletin, 61, 109-115. doi:10.1016/S0361-9230(03)00077-7
[63] McCulloch, J., Savaki, H.E. and Sokoloff, L. (1980) Influence of dopaminergic systems on the lateral habenular nucleus of the rat. Brain Research, 194, 117-124. doi:10.1016/0006-8993(80)91322-0

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