Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats
Open accessAbstract
Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate-putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40-80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate-putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cerebellum receives a dopaminergic pathway from the ventral tegmental area/substantia nigra pars compacta.
“The cerebellum receives a dopaminergic pathway from the ventral tegmental area/substantia nigra pars compacta [178].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [178]
Activation of the serotonergic system in inferior olive and cerebellum can enhance harmaline-induced tremor in animals, previously thought only attributable to olivocerebellar glutamate release acting on NMDAR and AMPAR.
“There is evidence that activation of the serotonergic system in the inferior olive and cerebellum can contribute to the enhancement of harmaline-induced tremor in animals, once thought to only be attributable to olivocerebellar release of glutamate acting on NMDAR and AMPAR [178].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [178]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689 · see citing works
Some observations upon a new inhibitor of monoamine oxidase in brain tissue
Johnston, J. P. (1968) · Biochemical Pharmacology · doi:10.1016/0006-2952(68)90066-x · Cited by 1,597 · see citing works
Männistö, P. T., & Kaakkola, S. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01423-6 · Cited by 1,068 · see citing works
The cerebellum communicates with the basal ganglia
Hoshi, E., Tremblay, L., Féger, J., Carras, P. L., & Strick, P. L. (2005) · Nature Neuroscience · doi:10.1038/nn1544 · Cited by 833 · see citing works
Samuels, E., & Szabadi, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908785777229 · Cited by 766 · see citing works
Llinas, R. H., & Yarom, Y. (1986) · The Journal of Physiology · doi:10.1113/jphysiol.1986.sp016147 · Cited by 668 · see citing works
The cerebral oscillatory network of parkinsonian resting tremor
Timmermann, L., Gross, J., Dirks, M., Volkmann, J., Freund, H.-J., & Schnitzler, A. (2003) · Brain · doi:10.1093/brain/awg022 · Cited by 544 · see citing works
Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists
Baraban, J. M., & Aghajanian, G. K. (1980) · Neuropharmacology · doi:10.1016/0028-3908(80)90187-2 · Cited by 442 · see citing works
Role of hyperactive cerebellum and motor cortex in Parkinson's disease
Yu, H., Sternad, D., Corcos, D. M., & Vaillancourt, D. E. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.11.047 · Cited by 436 · see citing works
Voogd, J., & Glickstein, M. (1998) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(98)01210-8 · Cited by 273 · see citing works
Mason, S. T., & Fibiger, H. C. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901870405 · Cited by 264 · see citing works
The pathophysiology of parkinsonian tremor: a review
Deuschl, G., Raethjen, J., Baron, R., Lindemann, M., Wilms, H., & Krack, P. (2000) · Journal of Neurology · doi:10.1007/pl00007781 · Cited by 251 · see citing works
Ikai, Y., Takada, M., Shinonaga, Y., & Mizuno, N. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90310-x · Cited by 210 · see citing works
Thalamic stimulation and suppression of parkinsonian tremor
Deiber, M., Pollak, P., Passingham, R. E., Landais, P., Gervason, C., Cinotti, L., Friston, K. J., Frackowiak, R. S. J., Mauguı̀ere, F., & Benabid, A. L. (1993) · Brain · doi:10.1093/brain/116.1.267 · Cited by 204 · see citing works
STRIATAL AMINES, EXPERIMENTAL TREMOR AND THE EFFECT OF HARMALINE IN THE MONKEY
POIRIER, L. J., Sourkes, T. L., BOUVIER, G., Boucher, R., & Carabin, S. (1966) · Brain · doi:10.1093/brain/89.1.37 · Cited by 202 · see citing works
Kizer, J. S., Palkovits, M., & Brownstein, M. (1976) · Brain Research · doi:10.1016/0006-8993(76)90192-x · Cited by 198 · see citing works
Pathologic findings in prospectively ascertained essential tremor subjects
Shill, H. A., Adler, C. H., Sabbagh, M. N., Connor, D. J., Caviness, J. N., Hentz, J. G., & Beach, T. G. (2008) · Neurology · doi:10.1212/01.wnl.0000310425.76205.02 · Cited by 194 · see citing works
Tremulous jaw movements in rats:a model of parkinsonian tremor
Salamone, J. D., Mayorga, A. J., Trevitt, J. T., Cousins, M. S., Conlan, A., & Nawab, A. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00053-7 · Cited by 161 · see citing works
Ichinohe, N., Mori, F., & Shoumura, K. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02744-x · Cited by 155 · see citing works
Melchitzky, D. S. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00139-6 · Cited by 146 · see citing works
Sugihara, I., Lang, E. J., & Llinas, R. H. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb00657.x · Cited by 146 · see citing works
Ossowska, K., Wardas, J., Śmiałowska, M., Kuter, K. Z., Lenda, T., Wierońska, J. M., Zieba, B. A., Nowak, P. G., Dąbrowska, J., Bortel, A. B., et al. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04301.x · Cited by 145 · see citing works
Self-citationMorphological differences in Parkinson’s disease with and without rest tremor
Benninger, D. H., Thees, S., Kollias, S., Bassetti, C. L., & Waldvogel, D. (2009) · Journal of Neurology · doi:10.1007/s00415-009-0092-2 · Cited by 139 · see citing works
Essential Tremor Associated With Focal Nonnigral Lewy Bodies
Louis, E. D., Honig, L. S., Vonsattel, J. P., Maraganore, D. M., Borden, S., & Moskowitz, C. B. (2005) · Archives of Neurology · doi:10.1001/archneur.62.6.1004 · Cited by 127 · see citing works
Harman (1-methyl-β-carboline) is a natural inhibitor of monoamine oxidase type A in rats
Rommelspacher, H., May, T., & Salewski, B. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90574-6 · Cited by 113 · see citing works
Miwa, H. (2006) · The Cerebellum · doi:10.1080/14734220601016080 · Cited by 106 · see citing works
Dopaminergic innervation and binding in the rat cerebellum
Panagopoulos, N. T., Papadopoulos, G. C., & Matsokis, N. A. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90398-d · Cited by 97 · see citing works
Fukuda, M., Barnes, A., Simon, E. S., Holmes, A., DHAWAN, V. M., Giladi, N., Fodstad, H., Ma, Y., & Eidelberg, D. (2003) · NeuroImage · doi:10.1016/j.neuroimage.2003.09.068 · Cited by 86 · see citing works
Baum, S. S., Hill, R., & Rommelspacher, H. (1996) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00543-2 · Cited by 83 · see citing works
Metabolic activity of cerebellar and basal ganglia-thalamic neurons is reduced in parkinsonism
Rolland, A., Herrero, M. T., García‐Martínez, V., Ruberg, M., Hirsch, É. C., & François, C. (2006) · Brain · doi:10.1093/brain/awl337 · Cited by 78 · see citing works
Milner, T. E., Cadoret, G., Lessard, L., & Smith, A. M. (1995) · Journal of Neurophysiology · doi:10.1152/jn.1995.73.6.2568 · Cited by 76 · see citing works
The indolaminergic innervation of the inferior olive. 2. Relation to harmaline induced tremor
Sjo¨lund, B., Bjo¨rklund, A., & Wiklund, L. (1977) · Brain Research · doi:10.1016/0006-8993(77)90026-9 · Cited by 74 · see citing works
Pharmacological characterization of harmaline-induced tremor activity in mice
Paterson, N. E., Malekiani, S. A., Foreman, M. M., Olivier, B., & Hanania, T. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.05.031 · Cited by 72 · see citing works
Saitow, F., Satake, S., Yamada, J., & Konishi, S. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.4.2016 · Cited by 71 · see citing works
Adell, A., Biggs, T. A. G., & MYERS, R. D. (1996) · Neuropharmacology · doi:10.1016/s0028-3908(96)00043-3 · Cited by 70 · see citing works
Hirono, M., & Obata, K. (2005) · Journal of Neurophysiology · doi:10.1152/jn.00711.2005 · Cited by 68 · see citing works
Batini, C., Buisseret-Delmas, C., & Conrath, M. (1981) · Experimental Brain Research · doi:10.1007/bf00237502 · Cited by 67 · see citing works
The cerebellar norepinephrine system: inhibition, modulation, and gating
Woodward, D. J., Moises, H. C., Waterhouse, B. D., Yeh, H. H., & Cheun, J. E. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63820-0 · Cited by 55 · see citing works
Beitz, A. J., & Saxon, D. W. (2004) · Journal of Neurocytology · doi:10.1023/b:neur.0000029648.81071.20 · Cited by 54 · see citing works
Wang, G., & Fowler, S. C. (2001) · Psychopharmacology · doi:10.1007/s002130100882 · Cited by 50 · see citing works
Differential expression of c-Fos following administration of two tremorgenic agents
Miwa, H., Nishi, K., Fuwa, T., & Mizuno, Y. (2000) · Neuroreport · doi:10.1097/00001756-200008030-00010 · Cited by 48 · see citing works
Fernando, J. C. R., Hoskins, B., & Ho, I. K. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90118-3 · Cited by 47 · see citing works
Roberts, V. J., Barth, S., Meunier, H., & Vale, W. (1996) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19960115)364:3 · Cited by 45 · see citing works
Yang, J., Sadler, T. R., Givrad, T. K., Maarek, J.-M. I., & Holschneider, D. P. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.03.010 · Cited by 41 · see citing works
Carlson, B. B., Wisniecki, A., & Salamone, J. D. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1247-3 · Cited by 39 · see citing works
Mehta, H. (2003) · Behavioural Brain Research · doi:10.1016/s0166-4328(03)00094-9 · Cited by 36 · see citing works
Significance of central noradrenergic system on harmaline induced tremor
Yamazaki, M., Tanaka, C., & Takaori, S. (1979) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(79)90207-7 · Cited by 35 · see citing works
Robinson, T. N., Souza, R. J. D., Cross, A. J., & Green, A. R. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb12656.x · Cited by 35 · see citing works
Citalopram, a selective serotonin reuptake inhibitor augments harmaline-induced tremor in rats
Arshaduddin, M., Kadasah, S., Biary, N. M., Deeb, S. A., Moutaery, K. A., & Tariq, M. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.10.035 · Cited by 34 · see citing works
Preclinical profile of befloxatone, a new reversible MAO-A inhibitor
Curet, O., Damoiseau, G., Sauvage, C., Sontag, N., Avenet, P., Depoortere, H., Caille, D., Bergis, O. E., & Scatton, B. (1998) · Journal of Affective Disorders · doi:10.1016/s0165-0327(98)00225-0 · Cited by 33 · see citing works
Pietraszek, M., Michaluk, J., Romańska, I., Wąsik, A., Gołembiowska, K., & Antkiewicz‐Michaluk, L. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9097-y · Cited by 33 · see citing works
Colzi, A., D'Agostini, F., Cesura, A. M., Borroni, E., & Prada, M. D. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38112-7 · Cited by 27 · see citing works
Tani, Y., Saito, K., Tsuneyoshi, A., Imoto, M., & Ohno, T. (1997) · Psychopharmacology · doi:10.1007/s002130050184 · Cited by 25 · see citing works
Effects of serotoninergic drugs on tremor induced by physostigmine in rats
Sarkar, S., Thomas, B., Muralikrishnan, D., & Mohanakumar, K. P. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00171-0 · Cited by 22 · see citing works
Role of the metabotropic glutamate receptor subtype 1 in the Harmaline-induced tremor in rats
Kolasiewicz, W., Kuter, K. Z., Wardas, J., & Ossowska, K. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0254-5 · Cited by 21 · see citing works
Self-citationPossible involvement of central pacemakers in clinical disorders of movement.
Mr, D. (1978) · PubMed · Cited by 21 · see citing works
Mohanakumar, K. P., Mitra, N., & Ganguly, D. K. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90175-9 · Cited by 17 · see citing works
Curet, O., Damoiseau, G., Labaune, J.-M., Rovel, V., & JARREAU, F. ‐. (1994) · Springer eBooks · doi:10.1007/978-3-7091-9324-2_46 · Cited by 16 · see citing works
Mehta, H., Thomas, B., & Mohanakumar, K. P. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01507-5 · Cited by 14 · see citing works
Mehta, H., Haobam, R., Rajamma, U., & Mohanakumar, K. P. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.05.002 · Cited by 14 · see citing works
Karai, N., Kato, T., Katsuyama, M., Nakamura, M., & Katsube, J. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90062-2 · Cited by 13 · see citing works
Exacerbation of harmaline-induced tremor by imipramine
Arshaduddin, M., Kadasah, S., Al-Deeb, S., Al-Moutaery, K. R., & TARIQ, M. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.01.014 · Cited by 13 · see citing works
[Harmaline-induced tremor and cerebral activities: labeling with 14C-2-deoxyglucose in the rat].
Batini, C., Buisseret-Delmas, C., & Conrath, M. (1978) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [31]Paxinos G Watson C The rat brain 1998 4 New York Academic Press
Cited by
Sorted by citations
Consensus Paper: Pathological Role of the Cerebellum in Autism
Fatemi, S. H., Aldinger, K. A., Ashwood, P., Bauman, M. L., Blaha, C. D., Blatt, G. J., Chauhan, A., Chauhan, V., Dager, S. R., Dickson, P. E., et al. (2012) · The Cerebellum · doi:10.1007/s12311-012-0355-9 · Cited by 723 · see citing works
Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor
Handforth, A. (2012) · Europe PMC (PubMed Central) · doi:10.7916/d8td9w2p · Cited by 93 · see citing works
Higarza, S. G., Arboleya, S., Gueimonde, M., Gómez-Lázaro, E., Arias, J. L., & Arias, N. (2019) · PLoS ONE · doi:10.1371/journal.pone.0223019 · Cited by 61 · see citing works
Neuroanatomical Heterogeneity of Essential Tremor According to Propranolol Response
Chung, S. J., Kwon, H., Lee, D.-K., Hong, J. Y., Sunwoo, M.-K., Sohn, Y. H., Lee, J., & Lee, P. H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084054 · Cited by 20 · see citing works
Hamed, S. A., & Abdellah, M. M. (2016) · International Journal of Neuroscience · doi:10.1080/00207454.2016.1181631 · Cited by 19 · see citing works
Kolasiewicz, W., Kuter, K. Z., Berghauzen-Maciejewska, K., Nowak, P. G., Schulze, G., & Ossowska, K. (2012) · Brain Research · doi:10.1016/j.brainres.2012.08.015 · Cited by 19 · see citing works
Self-citationOssowska, K., Wardas, J., Berghauzen-Maciejewska, K., Głowacka, U., Kuter, K. Z., Pilc, A., Zorn, S. H., & Doller, D. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.03.018 · Cited by 17 · see citing works
Self-citationGołembiowska, K., Berghauzen-Maciejewska, K., Górska, A. M., Kamińska, K., & Ossowska, K. (2013) · Brain Research · doi:10.1016/j.brainres.2013.08.059 · Cited by 12 · see citing works
Self-citationHarmaline toxicity on dorsal striatal neurons and its role in tremor
Zhan, X., Do, L. V., Zou, L. B., Zhan, R. S., Jones, M., Nawaz, S., & Manaye, K. F. (2023) · NeuroToxicology · doi:10.1016/j.neuro.2023.10.005 · Cited by 5 · see citing works
Use of the Harmaline and α1 Knockout Models to Identify Molecular Targets for Essential Tremor
Handforth, A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405195-9.00037-8 · Cited by 4 · see citing works
Mahani, F. D., Rajabi, S., Alehashem, M. S., Alaei, H., & Ramshini, E. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111479 · Cited by 5 · see citing works
Effect of Olfactory Manganese Dose on Motor Coordination in Iron-Deficient Rats
Kim, J. (2014) · MOJ Toxicology · doi:10.15406/mojt.2014.01.00001 · Cited by 2 · see citing works
Gonçalves, F. B., Garcia-Gomes, M. S., Sampaio, A. C. S., Kirsten, T. B., Bondan, E. F., Sandini, T. M., Flório, J. C., Lebrun, I., Coque, A. D. C., Alexandre-Ribeiro, S. R., et al. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114329 · Cited by 2 · see citing works
The Neuroanatomical Basis of the 5-HT Syndrome and Harmalineinduced Tremor
Lalonde, R., & Strazielle, C. (2023) · Current Clinical Pharmacology · doi:10.2174/2772432819666230703095203
- Authors
- Kolasiewicz, W., Kuter, K., Nowak, P., Pastuszka, A., & Ossowska, K.
- Affiliations
- Maj Institute of Pharmacology (PL)
- Medical University of Silesia (PL)
- Corresponding author
- Ossowska, Krystyna
- Venue
- The Cerebellum
- Published
- 2011-01-29
- Volume
- 10
- Issue
- 2
- Pages
- 267-280
- ISSN
- 1473-4222 (ISSN-L)
- 1473-4230
- PMC
- PMC3114101
- OpenAlex
- W1985593029
- Cited by
- 14
- References
- 63
- Citations by year
- 2025: 1 · 2023: 3 · 2019: 1 · 2016: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Cerebellum (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- harmaline-induced tremor, locus coeruleus, 6-hydroxydopamine lesion, desipramine, serotonin, 5-hydroxyindoleacetic acid, dopamine signaling, cerebellar vermis, tremor suppression, catecholaminergic system
- MeSH terms
- Central Nervous System Stimulants, Animals, Brain Chemistry, Cerebellum, Chromatography, High Pressure Liquid, Dopamine, Harmaline, Male, Neural Pathways, Synaptic Transmission, Norepinephrine, Serotonin, Tremor, Oxidopamine, Rats, Wistar, Adrenergic Agents, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
