Tags

Type your tag names separated by a space and hit enter

5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model.
Neurobiol Dis. 2013 Dec; 60:108-14.ND

Abstract

The serotonin system has recently emerged as an important player in the appearance of L-DOPA-induced dyskinesia (LID) in experimental models of Parkinson's disease, as it provides an unregulated source of L-DOPA-derived dopamine release in the dopamine-depleted striatum. Accordingly, toxin lesion or pharmacological silencing of serotonin neurons suppressed LID in the rat and monkey models of Parkinson's disease. However, 5-HT1 receptor agonists were also found to partially reduce the therapeutic effect of L-DOPA. In this study, we evaluated whether enhancement of the serotonin tone induced by the administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) could affect induction and expression of LID, as well as the therapeutic effect of L-DOPA, in 6-OHDA-lesioned rats. Drug naïve and L-DOPA-primed 6-OHDA-lesioned rats were chronically treated with a daily injection of L-DOPA (6 mg/kg plus benserazide, s.c.) alone, or in combination with 5-HTP (24-48 mg/kg, i.p.). The abnormal involuntary movements (AIMs) test, as well as the stepping and the motor activity tests, were performed during the chronic treatments. Results showed that 5-HTP reduced the appearance of LID of about 50% at both tested doses. A partial reduction of the therapeutic effect of L-DOPA was seen with the higher but not with the lower dose of 5-HTP. 5-HTP 24 mg/kg was also able to reduce the expression of dyskinesia in L-DOPA-primed dyskinetic rats, to a similar extent than in L-DOPA-primed rats. Importantly, the antidyskinetic effect of 5-HTP 24 mg/kg does not appear to be due to a competition with L-DOPA for crossing the blood-brain barrier; in fact, similar L-DOPA striatal levels were found in L-DOPA only and L-DOPA plus 5-HTP 24 mg/kg treated animals. These data further confirm the involvement of the serotonin system in the appearance of LID, and suggest that 5-HTP may be useful to counteract the appearance of dyskinesia in Parkinson's disease patients.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Tronci E
Department of Biomedical Sciences, Cagliari University, Cagliari, Italy.
Lisci C
No affiliation info available
Stancampiano R
No affiliation info available
Fidalgo C
No affiliation info available
Collu M
No affiliation info available
Devoto P
No affiliation info available
Carta M
No affiliation info available

MeSH

5-HydroxytryptophanAdrenergic AgentsAnimalsCaudate NucleusDisease Models, AnimalDopamineDyskinesia, Drug-InducedFemaleLevodopaMotor ActivityOxidopamineParkinsonian DisordersRatsRats, Sprague-DawleySerotonin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24004632

Citation

Tronci, Elisabetta, et al. "5-Hydroxy-tryptophan for the Treatment of L-DOPA-induced Dyskinesia in the Rat Parkinson's Disease Model." Neurobiology of Disease, vol. 60, 2013, pp. 108-14.
Tronci E, Lisci C, Stancampiano R, et al. 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model. Neurobiol Dis. 2013;60:108-14.
Tronci, E., Lisci, C., Stancampiano, R., Fidalgo, C., Collu, M., Devoto, P., & Carta, M. (2013). 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model. Neurobiology of Disease, 60, 108-14. https://doi.org/10.1016/j.nbd.2013.08.014
Tronci E, et al. 5-Hydroxy-tryptophan for the Treatment of L-DOPA-induced Dyskinesia in the Rat Parkinson's Disease Model. Neurobiol Dis. 2013;60:108-14. PubMed PMID: 24004632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model. AU - Tronci,Elisabetta, AU - Lisci,Carlo, AU - Stancampiano,Roberto, AU - Fidalgo,Camino, AU - Collu,Maria, AU - Devoto,Paola, AU - Carta,Manolo, Y1 - 2013/09/01/ PY - 2013/07/02/received PY - 2013/08/20/revised PY - 2013/08/24/accepted PY - 2013/9/6/entrez PY - 2013/9/6/pubmed PY - 2014/6/16/medline KW - 5-HTP KW - 5-hydroxy-tryptophan KW - 6-OHDA KW - 6-hydroxy-dopamine KW - AIMs KW - DA KW - Dopamine KW - Dyskinesia KW - LID KW - PD KW - Parkinson's disease KW - SSRIs KW - Serotonin KW - TH KW - abnormal involuntary movements KW - dopamine KW - l-DOPA KW - l-DOPA-induced dyskinesia KW - serotonin reuptake inhibitors KW - tyrosine hydroxylase SP - 108 EP - 14 JF - Neurobiology of disease JO - Neurobiol Dis VL - 60 N2 - The serotonin system has recently emerged as an important player in the appearance of L-DOPA-induced dyskinesia (LID) in experimental models of Parkinson's disease, as it provides an unregulated source of L-DOPA-derived dopamine release in the dopamine-depleted striatum. Accordingly, toxin lesion or pharmacological silencing of serotonin neurons suppressed LID in the rat and monkey models of Parkinson's disease. However, 5-HT1 receptor agonists were also found to partially reduce the therapeutic effect of L-DOPA. In this study, we evaluated whether enhancement of the serotonin tone induced by the administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) could affect induction and expression of LID, as well as the therapeutic effect of L-DOPA, in 6-OHDA-lesioned rats. Drug naïve and L-DOPA-primed 6-OHDA-lesioned rats were chronically treated with a daily injection of L-DOPA (6 mg/kg plus benserazide, s.c.) alone, or in combination with 5-HTP (24-48 mg/kg, i.p.). The abnormal involuntary movements (AIMs) test, as well as the stepping and the motor activity tests, were performed during the chronic treatments. Results showed that 5-HTP reduced the appearance of LID of about 50% at both tested doses. A partial reduction of the therapeutic effect of L-DOPA was seen with the higher but not with the lower dose of 5-HTP. 5-HTP 24 mg/kg was also able to reduce the expression of dyskinesia in L-DOPA-primed dyskinetic rats, to a similar extent than in L-DOPA-primed rats. Importantly, the antidyskinetic effect of 5-HTP 24 mg/kg does not appear to be due to a competition with L-DOPA for crossing the blood-brain barrier; in fact, similar L-DOPA striatal levels were found in L-DOPA only and L-DOPA plus 5-HTP 24 mg/kg treated animals. These data further confirm the involvement of the serotonin system in the appearance of LID, and suggest that 5-HTP may be useful to counteract the appearance of dyskinesia in Parkinson's disease patients. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/24004632/5_Hydroxy_tryptophan_for_the_treatment_of_L_DOPA_induced_dyskinesia_in_the_rat_Parkinson's_disease_model_ DB - PRIME DP - Unbound Medicine ER -