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Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours.
Eur J Neurosci. 2005 Jan; 21(1):179-86.EJ

Abstract

BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.

Authors+Show Affiliations

Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London SE1 1UL, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15654855

Citation

Lane, E L., et al. "Repeated Administration of the Monoamine Reuptake Inhibitor BTS 74 398 Induces Ipsilateral Circling in the 6-hydroxydopamine Lesioned Rat Without Sensitizing Motor Behaviours." The European Journal of Neuroscience, vol. 21, no. 1, 2005, pp. 179-86.
Lane EL, Cheetham SC, Jenner P. Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours. Eur J Neurosci. 2005;21(1):179-86.
Lane, E. L., Cheetham, S. C., & Jenner, P. (2005). Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours. The European Journal of Neuroscience, 21(1), 179-86.
Lane EL, Cheetham SC, Jenner P. Repeated Administration of the Monoamine Reuptake Inhibitor BTS 74 398 Induces Ipsilateral Circling in the 6-hydroxydopamine Lesioned Rat Without Sensitizing Motor Behaviours. Eur J Neurosci. 2005;21(1):179-86. PubMed PMID: 15654855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6-hydroxydopamine lesioned rat without sensitizing motor behaviours. AU - Lane,E L, AU - Cheetham,S C, AU - Jenner,P, PY - 2005/1/19/pubmed PY - 2005/3/30/medline PY - 2005/1/19/entrez SP - 179 EP - 86 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 21 IS - 1 N2 - BTS 74 398 (1-[1-(3,4-dichlorophenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6-hydroxydopamine (6-OHDA)-lesioned rats for the production of abnormal motor behaviours and the induction of striatal DeltaFosB were determined in comparison with l-3,4-dihydroxyphenylalanine methyl ester (L-dopa). Acute administration of BTS 74 398 induced a dose-dependent ipsilateral circling response in unilaterally 6-OHDA-lesioned rats whereas L-dopa produced dose-dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, L-dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both L-dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In L-dopa-treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6-OHDA-lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal DeltaFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by L-dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/15654855/Repeated_administration_of_the_monoamine_reuptake_inhibitor_BTS_74_398_induces_ipsilateral_circling_in_the_6_hydroxydopamine_lesioned_rat_without_sensitizing_motor_behaviours_ L2 - https://doi.org/10.1111/j.1460-9568.2004.03834.x DB - PRIME DP - Unbound Medicine ER -