L-Dopa and Brain Serotonin System Dysfunction
Abstract
:1. Introduction
2. l-Dopa Treatment in PD
2.1. l-Dopa and the 5-HT System
2.2. l-Dopa Induced Dopamine Production within 5-HT Neurons
2.3. 5-HT Neurons and l-Dopa Induced Dyskinesia
3. l-Dopa Induced 5-HTergic Deficits
Model | l-Dopa concentration (mg/kg/day) | Treatment duration (days) | 5-HTerigc deficit(s) | Brain region(s) affected | Reference |
---|---|---|---|---|---|
Rat (non-lesioned) | 250 | 60 | ↓ 5-HT tissue content | STR, Cortex | Borah and Mohanakumar [63] |
Rat (unilateral 6-OHDA) | 12 | 10 | ↓ 5-HT tissue content | STR, Cortex STR, HIPP, SNr, PFC | Navailles et al. [65] |
Rat (unilateral 6-OHDA) | 12 | 28 | ↓ 5-HT tissue content | Amygdala | Eskow-Jaunarajs et al. [66] |
Rat (bilateral 6-OHDA) | 12 | 75 | ↓ 5-HT tissue content | STR, Amygdala, PFC | Eskow-Jaunarajs et al. [58] |
Rat (non-lesioned) | 12 | 10 | ↓ 5-HT cell bodies | Dorsal DRN | Stansley and Yamamoto [17] |
Macaque (MPTP-lesioned) | 40 | ~90 (3 months) | ↓ 5-HT tissue content | STR, Motor cortex, HIPP, Amygdala | Engeln et al. [67] |
4. Behavioral Implications of l-Dopa Induced 5-HTergic Deficits
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Kasten, M.; Chade, A.; Tanner, C.M. Epidemiology of Parkinson’s disease. Handb. Clin. Neurol. 2007, 83, 129–151. [Google Scholar] [PubMed]
- Hornykiewicz, O. Brain monoamines and Parkinsonism. Psychopharmacol. Bull. 1975, 11, 34–35. [Google Scholar] [PubMed]
- Yamamoto, B.K.; Freed, C.R. The trained circling rat: A model for inducing unilateral caudate dopamine metabolism. Nature 1982, 298, 467–468. [Google Scholar] [CrossRef] [PubMed]
- Hoehn, M.M.; Yahr, M.D. Parkinsonism: Onset, progression and mortality. Neurology 1967, 17, 427–442. [Google Scholar] [CrossRef] [PubMed]
- Gray, R.; Ives, N.; Rick, C.; Patel, S.; Gray, A.; Jenkinson, C.; McIntosh, E.; Wheatley, K.; Williams, A.; Clarke, C.E. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): A large, open-label, pragmatic randomised trial. Lancet 2014, 384, 1196–1205. [Google Scholar] [CrossRef] [PubMed]
- Seiden, L.S.; Carlsson, A. Temporary and partial antagonism by l-Dopa of reserpine-induced suppression of a conditioned avoidance response. Psychopharmacologia 1963, 4, 418–423. [Google Scholar] [CrossRef] [PubMed]
- Cotzias, G.C. l-Dopa for Parkinsonism. N. Engl. J. Med. 1968, 278, 630. [Google Scholar] [PubMed]
- Barbeau, A.; Mars, H.; Gillo-Joffroy, L. Adverse clinical side effects of levodopa therapy. Contemp. Neurol. Ser. 1971, 8, 203–237. [Google Scholar] [PubMed]
- Banerjee, A.K.; Falkai, P.G.; Savidge, M. Visual hallucinations in the elderly associated with the use of levodopa. Postgrad. Med. J. 1989, 65, 358–361. [Google Scholar] [CrossRef] [PubMed]
- Chaudhuri, K.R.; Healy, D.G.; Schapira, A.H. Non-motor symptoms of Parkinson’s disease: Diagnosis and management. Lancet Neurol. 2006, 5, 235–245. [Google Scholar] [CrossRef] [PubMed]
- Choi, C.; Sohn, Y.H.; Lee, J.H.; Kim, J. The effect of long-term levodopa therapy on depression level in de novo patients with Parkinson’s disease. J. Neurol. Sci. 2000, 172, 12–16. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.J.; Park, S.Y.; Cho, Y.J.; Hong, K.S.; Cho, J.Y.; Seo, S.Y.; Lee, D.H.; Jeon, B.S. Nonmotor symptoms in de novo Parkinson disease before and after dopaminergic treatment. J. Neurol. Sci. 2009, 287, 200–204. [Google Scholar] [CrossRef] [PubMed]
- Richard, I.H.; Frank, S.; McDermott, M.P.; Wang, H.; Justus, A.W.; LaDonna, K.A.; Kurlan, R. The ups and downs of Parkinson disease: A prospective study of mood and anxiety fluctuations. Cogn. Behav. Neurol. 2004, 17, 201–207. [Google Scholar] [PubMed]
- Stansley, B.J.; Yamamoto, B.K. l-dopa-induced dopamine synthesis and oxidative stress in serotonergic cells. Neuropharmacology 2013, 67, 243–251. [Google Scholar] [CrossRef] [PubMed]
- Ng, K.Y.; Chase, T.N.; Colburn, R.W.; Kopin, I.J. l-Dopa-induced release of cerebral monoamines. Science 1970, 170, 76–77. [Google Scholar] [CrossRef] [PubMed]
- Miller, D.W.; Abercrombie, E.D. Role of high-affinity dopamine uptake and impulse activity in the appearance of extracellular dopamine in striatum after administration of exogenous l-DOPA: Studies in intact and 6-hydroxydopamine-treated rats. J. Neurochem. 1999, 72, 1516–1522. [Google Scholar] [CrossRef] [PubMed]
- Stansley, B.J.; Yamamoto, B.K. Chronic l-dopa decreases serotonin neurons in a subregion of the dorsal raphe nucleus. J. Pharmacol. Exp. Ther. 2014, 351, 440–447. [Google Scholar] [CrossRef] [PubMed]
- Nutt, J.G.; Fellman, J.H. Pharmacokinetics of levodopa. Clin. Neuropharmacol. 1984, 7, 35–49. [Google Scholar] [CrossRef] [PubMed]
- Nutt, J.G.; Woodward, W.R.; Anderson, J.L. The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: The mechanism of action in the treatment of parkinsonism. Ann. Neurol. 1985, 18, 537–543. [Google Scholar] [CrossRef] [PubMed]
- Wade, L.A.; Katzman, R. Synthetic amino acids and the nature of l-DOPA transport at the blood-brain barrier. J. Neurochem. 1975, 25, 837–842. [Google Scholar] [CrossRef] [PubMed]
- Pardridge, W.M. Brain metabolism: A perspective from the blood-brain barrier. Physiol. Rev. 1983, 63, 1481–1535. [Google Scholar] [PubMed]
- Navailles, S.; Bioulac, B.; Gross, C.; de Deurwaerdere, P. Serotonergic neurons mediate ectopic release of dopamine induced by l-DOPA in a rat model of Parkinson’s disease. Neurobiol. Dis. 2010, 38, 136–143. [Google Scholar] [CrossRef] [PubMed]
- Juorio, A.V.; Li, X.M.; Walz, W.; Paterson, I.A. Decarboxylation of l-dopa by cultured mouse astrocytes. Brain Res. 1993, 626, 306–309. [Google Scholar] [CrossRef] [PubMed]
- Arai, R.; Karasawa, N.; Geffard, M.; Nagatsu, T.; Nagatsu, I. Immunohistochemical evidence that central serotonin neurons produce dopamine from exogenous l-DOPA in the rat, with reference to the involvement of aromatic l-amino acid decarboxylase. Brain Res. 1994, 667, 295–299. [Google Scholar] [CrossRef] [PubMed]
- Christenson, J.G.; Dairman, W.; Udenfriend, S. On the identity of DOPA decarboxylase and 5-hydroxytryptophan decarboxylase (immunological titration-aromatic l-amino acid decarboxylase-serotonin-dopamine-norepinephrine). Proc. Natl. Acad. Sci. USA 1972, 69, 343–347. [Google Scholar] [CrossRef] [PubMed]
- Ugrumov, M.V. Non-dopaminergic neurons partly expressing dopaminergic phenotype: Distribution in the brain, development and functional significance. J. Chem. Neuroanat. 2009, 38, 241–256. [Google Scholar] [CrossRef] [PubMed]
- Ng, L.K.; Colburn, R.W.; Kopin, I.J. Effects of l-dopa on accumulation and efflux of monoamines in particles of rat brain homogenates. J. Pharmacol. Exp. Ther. 1972, 183, 316–325. [Google Scholar] [PubMed]
- Hollister, A.S.; Breese, G.R.; Mueller, R.A. Role of monoamine neural systems in l-dihydroxyphenylalanine-stimulated activity. J. Pharmacol. Exp. Ther. 1979, 208, 37–43. [Google Scholar] [PubMed]
- Tanaka, H.; Kannari, K.; Maeda, T.; Tomiyama, M.; Suda, T.; Matsunaga, M. Role of serotonergic neurons in l-DOPA-derived extracellular dopamine in the striatum of 6-OHDA-lesioned rats. Neuroreport 1999, 10, 631–634. [Google Scholar] [CrossRef] [PubMed]
- Kannari, K.; Yamato, H.; Shen, H.; Tomiyama, M.; Suda, T.; Matsunaga, M. Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered l-DOPA in the striatum with nigrostriatal denervation. J. Neurochem. 2001, 76, 1346–1353. [Google Scholar] [CrossRef] [PubMed]
- Descarries, L.; Audet, M.A.; Doucet, G.; Garcia, S.; Oleskevich, S.; Seguela, P.; Soghomonian, J.J.; Watkins, K.C. Morphology of central serotonin neurons. Brief review of quantified aspects of their distribution and ultrastructural relationships. Ann. N. Y. Acad. Sci. 1990, 600, 81–92. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, B.L.; Azmitia, E.C. Structure and function of the brain serotonin system. Physiol. Rev. 1992, 72, 165–229. [Google Scholar] [PubMed]
- Hornung, J.P. The human raphe nuclei and the serotonergic system. J. Chem. Neuroanat. 2003, 26, 331–343. [Google Scholar] [CrossRef] [PubMed]
- Huot, P.; Fox, S.H.; Brotchie, J.M. The serotonergic system in Parkinson’s disease. Prog. Neurobiol. 2011, 95, 163–212. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, B.L.; Foote, S.L.; Bloom, F.E. Differential projections of neurons within the dorsal raphe nucleus of the rat: A horseradish peroxidase (HRP) study. Brain Res. 1978, 147, 149–153. [Google Scholar] [CrossRef] [PubMed]
- Calizo, L.H.; Akanwa, A.; Ma, X.; Pan, Y.Z.; Lemos, J.C.; Craige, C.; Heemstra, L.A.; Beck, S.G. Raphe serotonin neurons are not homogenous: Electrophysiological, morphological and neurochemical evidence. Neuropharmacology 2011, 61, 524–543. [Google Scholar] [CrossRef] [PubMed]
- Lowry, C.; Evans, A.; Gasser, P.; Hale, M.; Staub, D.; Shekhar, A. Topographic organization and chemoarchitecture of the dorsal raphe nucleus. In Serotonin and Sleep: Molecular, Functional and Clinical Aspects; Monti, J., Pandi-Perumal, S.R., Jacobs, B., Nutt, D., Eds.; Birkhäuser Verlag: Basel, Switzerland, 2008; pp. 25–67. [Google Scholar]
- Lowry, C.A.; Hale, M.W.; Evans, A.K.; Heerkens, J.; Staub, D.R.; Gasser, P.J.; Shekhar, A. Serotonergic systems, anxiety, and affective disorder: Focus on the dorsomedial part of the dorsal raphe nucleus. Ann. N. Y. Acad. Sci. 2008, 1148, 86–94. [Google Scholar] [CrossRef] [PubMed]
- Yee, R.E.; Cheng, D.W.; Huang, S.C.; Namavari, M.; Satyamurthy, N.; Barrio, J.R. Blood-brain barrier and neuronal membrane transport of 6-[18F]fluoro-l-DOPA. Biochem. Pharmacol. 2001, 62, 1409–1415. [Google Scholar] [CrossRef] [PubMed]
- Arai, R.; Karasawa, N.; Nagatsu, I. Aromatic l-amino acid decarboxylase is present in serotonergic fibers of the striatum of the rat. A double-labeling immunofluorescence study. Brain Res. 1996, 706, 177–179. [Google Scholar] [CrossRef] [PubMed]
- Erickson, J.D.; Schafer, M.K.; Bonner, T.I.; Eiden, L.E.; Weihe, E. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc. Natl. Acad. Sci. USA 1996, 93, 5166–5171. [Google Scholar] [CrossRef] [PubMed]
- Abercrombie, E.D.; Bonatz, A.E.; Zigmond, M.J. Effects of l-dopa on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats. Brain Res. 1990, 525, 36–44. [Google Scholar] [CrossRef] [PubMed]
- Maeda, T.; Nagata, K.; Yoshida, Y.; Kannari, K. Serotonergic hyperinnervation into the dopaminergic denervated striatum compensates for dopamine conversion from exogenously administered l-DOPA. Brain Res. 2005, 1046, 230–233. [Google Scholar] [CrossRef] [PubMed]
- Yamada, H.; Aimi, Y.; Nagatsu, I.; Taki, K.; Kudo, M.; Arai, R. Immunohistochemical detection of l-DOPA-derived dopamine within serotonergic fibers in the striatum and the substantia nigra pars reticulata in Parkinsonian model rats. Neurosci. Res. 2007, 59, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Lindgren, H.S.; Andersson, D.R.; Lagerkvist, S.; Nissbrandt, H.; Cenci, M.A. l-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: Temporal and quantitative relationship to the expression of dyskinesia. J. Neurochem. 2010, 112, 1465–1476. [Google Scholar] [CrossRef] [PubMed]
- Bezard, E.; Brotchie, J.M.; Gross, C.E. Pathophysiology of levodopa-induced dyskinesia: Potential for new therapies. Nat. Rev. Neurosci. 2001, 2, 577–588. [Google Scholar] [CrossRef] [PubMed]
- Encarnacion, E.V.; Hauser, R.A. Levodopa-induced dyskinesias in Parkinson’s disease: Etiology, impact on quality of life, and treatments. Eur. Neurol. 2008, 60, 57–66. [Google Scholar] [CrossRef] [PubMed]
- Rylander, D.; Parent, M.; O’Sullivan, S.S.; Dovero, S.; Lees, A.J.; Bezard, E.; Descarries, L.; Cenci, M.A. Maladaptive plasticity of serotonin axon terminals in levodopa-induced dyskinesia. Ann. Neurol. 2010, 68, 619–628. [Google Scholar] [CrossRef] [PubMed]
- Carta, M.; Carlsson, T.; Kirik, D.; Bjorklund, A. Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats. Brain 2007, 130, 1819–1833. [Google Scholar] [CrossRef] [PubMed]
- Politis, M.; Wu, K.; Loane, C.; Brooks, D.J.; Kiferle, L.; Turkheimer, F.E.; Bain, P.; Molloy, S.; Piccini, P. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients. J. Clin. Investig. 2014, 124, 1340–1349. [Google Scholar] [CrossRef] [PubMed]
- Cenci, M.A. Presynaptic mechanisms of l-DOPA-induced dyskinesia: The findings, the debate, and the therapeutic implications. Front. Neurol. 2014, 5, 242. [Google Scholar] [CrossRef] [PubMed]
- Graham, D.G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol. Pharmacol. 1978, 14, 633–643. [Google Scholar] [PubMed]
- Berman, S.B.; Hastings, T.G. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: Implications for Parkinson’s disease. J. Neurochem. 1999, 73, 1127–1137. [Google Scholar] [CrossRef] [PubMed]
- Kuhn, D.M.; Arthur, R., Jr. Dopamine inactivates tryptophan hydroxylase and forms a redox-cycling quinoprotein: Possible endogenous toxin to serotonin neurons. J. Neurosci. 1998, 18, 7111–7117. [Google Scholar] [PubMed]
- Mena, M.A.; Pardo, B.; Casarejos, M.J.; Fahn, S.; Garcia de Yebenes, J. Neurotoxicity of levodopa on catecholamine-rich neurons. Mov. Disord. 1992, 7, 23–31. [Google Scholar] [CrossRef] [PubMed]
- Eskow Jaunarajs, K.L.; Angoa-Perez, M.; Kuhn, D.M.; Bishop, C. Potential mechanisms underlying anxiety and depression in Parkinson’s disease: Consequences of l-DOPA treatment. Neurosci. Biobehav. Rev. 2011, 35, 556–564. [Google Scholar]
- Cheshire, P.; Ayton, S.; Bertram, K.L.; Ling, H.; Li, A.; McLean, C.; Halliday, G.M.; O’Sullivan, S.S.; Revesz, T.; Finkelstein, D.I.; et al. Serotonergic markers in Parkinson’s disease and levodopa-induced dyskinesias. Mov. Disord. 2015. [Google Scholar] [CrossRef]
- Eskow Jaunarajs, K.L.; George, J.A.; Bishop, C. l-DOPA-induced dyregulation of extrastriatal dopamine and serotonin and affective symptoms in a bilateral rat model of Parkinson’s disease. Neuroscience 2012, 218, 243–256. [Google Scholar]
- Perry, T.L.; Yong, V.W.; Ito, M.; Foulks, J.G.; Wall, R.A.; Godin, D.V.; Clavier, R.M. Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of l-DOPA and carbidopa chronically. J. Neurochem. 1984, 43, 990–993. [Google Scholar] [CrossRef] [PubMed]
- Fornai, F.; Battaglia, G.; Gesi, M.; Giorgi, F.S.; Orzi, F.; Nicoletti, F.; Ruggieri, S. Time-course and dose-response study on the effects of chronic l-DOPA administration on striatal dopamine levels and dopamine transporter following MPTP toxicity. Brain Res. 2000, 887, 110–117. [Google Scholar] [CrossRef] [PubMed]
- Zhu, M.Y.; Juorio, A.V.; Paterson, I.A.; Boulton, A.A. Regulation of aromatic l-amino acid decarboxylase in rat striatal synaptosomes: Effects of dopamine receptor agonists and antagonists. Br. J. Pharmacol. 1994, 112, 23–30. [Google Scholar] [CrossRef] [PubMed]
- Cumming, R.G.; Salkeld, G.; Thomas, M.; Szonyi, G. Prospective study of the impact of fear of falling on activities of daily living, SF-36 scores, and nursing home admission. J. Gerontol. A Biol. Sci. Med. Sci. 2000, 55, M299–M305. [Google Scholar] [CrossRef] [PubMed]
- Borah, A.; Mohanakumar, K.P. Long-term l-DOPA treatment causes indiscriminate increase in dopamine levels at the cost of serotonin synthesis in discrete brain regions of rats. Cell. Mol. Neurobiol. 2007, 27, 985–996. [Google Scholar] [CrossRef] [PubMed]
- Ng, L.K.; Chase, T.N.; Colburn, R.W.; Kopin, I.J. l-dopa in Parkinsonism. A possible mechanism of action. Neurology 1972, 22, 688–696. [Google Scholar] [CrossRef] [PubMed]
- Navailles, S.; Bioulac, B.; Gross, C.; de Deurwaerdere, P. Chronic l-DOPA therapy alters central serotonergic function and l-DOPA-induced dopamine release in a region-dependent manner in a rat model of Parkinson’s disease. Neurobiol. Dis. 2011, 41, 585–590. [Google Scholar] [CrossRef] [PubMed]
- Eskow Jaunarajs, K.L.; Dupre, K.B.; Ostock, C.Y.; Button, T.; Deak, T.; Bishop, C. Behavioral and neurochemical effects of chronic l-DOPA treatment on nonmotor sequelae in the hemiparkinsonian rat. Behav. Pharmacol. 2010, 21, 627–637. [Google Scholar]
- Engeln, M.; de Deurwaerdere, P.; Li, Q.; Bezard, E.; Fernagut, P.O. Widespread monoaminergic dysregulation of both motor and non-motor circuits in Parkinsonism and Dyskinesia. Cereb Cortex 2014. [Epub ahead of print]. [Google Scholar]
- Pahwa, R.; Lyons, K.E. Levodopa-related wearing-off in Parkinson’s disease: Identification and management. Curr. Med. Res. Opin. 2009, 25, 841–849. [Google Scholar] [CrossRef] [PubMed]
- Jasinska, A.J.; Perkins, S.C. Impact of the tri-allelic serotonin transporter polymorphism on the white-matter tract connecting the amygdala and the prefrontal cortex. J. Neurosci. 2009, 29, 10461–10462. [Google Scholar] [CrossRef] [PubMed]
- Bhidayasiri, R.; Truong, D.D. Therapeutic strategies for nonmotor symptoms in early Parkinson’s disease: The case for a higher priority and stronger evidence. Parkinsonism Relat. Disord. 2012, 18 (Suppl. 1), S110–S113. [Google Scholar] [CrossRef] [PubMed]
- Maier, S.F.; Watkins, L.R. Stressor controllability and learned helplessness: The roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci. Biobehav. Rev. 2005, 29, 829–841. [Google Scholar] [CrossRef] [PubMed]
- Pietruszewska, I.; Jasinska, M.; Lewicka-Wysocka, H.; Marcjan, K.; Stencka, K. Urinary excretion of 5-hydroxyindoleacetic acid and serum tryptophan and serotonin levels in patients with depression. Psychiatr. Pol. 1984, 18, 9–16. [Google Scholar] [PubMed]
- Amat, J.; Baratta, M.V.; Paul, E.; Bland, S.T.; Watkins, L.R.; Maier, S.F. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat. Neurosci. 2005, 8, 365–371. [Google Scholar] [CrossRef] [PubMed]
- Grahn, R.E.; Will, M.J.; Hammack, S.E.; Maswood, S.; McQueen, M.B.; Watkins, L.R.; Maier, S.F. Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor. Brain Res. 1999, 826, 35–43. [Google Scholar] [CrossRef] [PubMed]
- Lowry, C.A.; Johnson, P.L.; Hay-Schmidt, A.; Mikkelsen, J.; Shekhar, A. Modulation of anxiety circuits by serotonergic systems. Stress 2005, 8, 233–246. [Google Scholar] [CrossRef] [PubMed]
- Politis, M.; Wu, K.; Loane, C.; Quinn, N.P.; Brooks, D.J.; Oertel, W.H.; Bjorklund, A.; Lindvall, O.; Piccini, P. Serotonin neuron loss and nonmotor symptoms continue in Parkinson’s patients treated with dopamine grafts. Sci. Transl. Med. 2012, 4, 128ra141. [Google Scholar] [CrossRef]
- Schrag, A. Quality of life and depression in Parkinson’s disease. J. Neurol. Sci. 2006, 248, 151–157. [Google Scholar] [CrossRef] [PubMed]
- Rylander, R. Organic dust induced pulmonary disease—The role of mould derived beta-glucan. Ann. Agric. Environ. Med. 2010, 17, 9–13. [Google Scholar] [PubMed]
- Braak, H.; Del Tredici, K.; Rub, U.; de Vos, R.A.; Jansen Steur, E.N.; Braak, E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 2003, 24, 197–211. [Google Scholar] [CrossRef] [PubMed]
- Paulus, W.; Jellinger, K. The neuropathologic basis of different clinical subgroups of Parkinson’s disease. J. Neuropathol. Exp. Neurol. 1991, 50, 743–755. [Google Scholar] [CrossRef] [PubMed]
- Marsh, G.G.; Markham, C.H. Does levodopa alter depression and psychopathology in Parkinsonism patients? J. Neurol. Neurosurg. Psychiatry 1973, 36, 925–935. [Google Scholar] [CrossRef] [PubMed]
- Reed, M.C.; Nijhout, H.F.; Best, J. Computational studies of the role of serotonin in the basal ganglia. Front. Integr. Neurosci. 2013, 7, 41. [Google Scholar] [CrossRef] [PubMed]
- Winstanley, C.A.; Theobald, D.E.; Dalley, J.W.; Robbins, T.W. Interactions between serotonin and dopamine in the control of impulsive choice in rats: Therapeutic implications for impulse control disorders. Neuropsychopharmacology 2005, 30, 669–682. [Google Scholar] [PubMed]
- Jasinska, A.J.; Ho, S.S.; Taylor, S.F.; Burmeister, M.; Villafuerte, S.; Polk, T.A. Influence of threat and serotonin transporter genotype on interference effects. Front. Psychol. 2012, 3, 139. [Google Scholar] [PubMed]
- Jasinska, A.J.; Lowry, C.A.; Burmeister, M. Corrigendum: Serotonin transporter gene, stress, and raphe-raphe interactions: A molecular mechanism of depression. Trends Neurosci. 2012, 35, 454–455. [Google Scholar] [CrossRef] [PubMed]
- Tronci, E.; Lisci, C.; Stancampiano, R.; Fidalgo, C.; Collu, M.; Devoto, P.; Carta, M. 5-Hydroxy-tryptophan for the treatment of l-DOPA-induced dyskinesia in the rat Parkinson’s disease model. Neurobiol. Dis. 2013, 60, 108–114. [Google Scholar] [CrossRef] [PubMed]
- Owen, A.M. Cognitive dysfunction in Parkinson’s disease: The role of frontostriatal circuitry. Neuroscientist 2004, 10, 525–537. [Google Scholar] [CrossRef] [PubMed]
- Rabey, J.M.; Vardi, J.; Askenazi, J.J.; Streifler, M. l-tryptophan administration in l-dopa-induced hallucinations in elderly Parkinsonian patients. Gerontology 1977, 23, 438–444. [Google Scholar] [CrossRef] [PubMed]
- Rosenkranz, J.A.; Grace, A.A. Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo. J. Neurosci. 2002, 22, 324–337. [Google Scholar] [PubMed]
- Albert, P.R.; Vahid-Ansari, F.; Luckhart, C. Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: Pivotal role of pre- and post-synaptic 5-HT1A receptor expression. Front. Behav. Neurosci. 2014, 8, 199. [Google Scholar] [CrossRef] [PubMed]
- Izumi, T.; Ohmura, Y.; Futami, Y.; Matsuzaki, H.; Kubo, Y.; Yoshida, T.; Yoshioka, M. Effects of serotonergic terminal lesion in the amygdala on conditioned fear and innate fear in rats. Eur. J. Pharmacol. 2012, 696, 89–95. [Google Scholar] [CrossRef] [PubMed]
- van Asselen, M.; Kessels, R.P.; Neggers, S.F.; Kappelle, L.J.; Frijns, C.J.; Postma, A. Brain areas involved in spatial working memory. Neuropsychologia 2006, 44, 1185–1194. [Google Scholar]
- Santiago, R.M.; Barbiero, J.; Gradowski, R.W.; Bochen, S.; Lima, M.M.; Da Cunha, C.; Andreatini, R.; Vital, M.A. Induction of depressive-like behavior by intranigral 6-OHDA is directly correlated with deficits in striatal dopamine and hippocampal serotonin. Behav. Brain Res. 2014, 259, 70–77. [Google Scholar] [CrossRef] [PubMed]
- Winter, C.; von Rumohr, A.; Mundt, A.; Petrus, D.; Klein, J.; Lee, T.; Morgenstern, R.; Kupsch, A.; Juckel, G. Lesions of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area enhance depressive-like behavior in rats. Behav. Brain Res. 2007, 184, 133–141. [Google Scholar] [CrossRef] [PubMed]
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Stansley, B.J.; Yamamoto, B.K. L-Dopa and Brain Serotonin System Dysfunction. Toxics 2015, 3, 75-88. https://doi.org/10.3390/toxics3010075
Stansley BJ, Yamamoto BK. L-Dopa and Brain Serotonin System Dysfunction. Toxics. 2015; 3(1):75-88. https://doi.org/10.3390/toxics3010075
Chicago/Turabian StyleStansley, Branden J., and Bryan K. Yamamoto. 2015. "L-Dopa and Brain Serotonin System Dysfunction" Toxics 3, no. 1: 75-88. https://doi.org/10.3390/toxics3010075