Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model

S. T. Warraich, H. N. Allbutt, R. Billing, J. Radford, M. J. Coster, M. Kassiou, J. M. Henderson*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats. Parkinsonism and the efficacy of drugs were assessed using a battery of behavioural tests including balance beam, apomorphine-induced rotation, body axis bias or "curling", head position bias and disengage sensorimotor latency test. Immunohistochemistry was performed on post-mortem tissue to estimate the loss of dopaminergic neurons. The main effects were that BZAD-01 co-administration prevented chronic levodopa-induced potentiation of apomorphine rotation. However levodopa-treated rats were slower than either controls or BZAD-01-treated rats in the locomotor test. The improvement in the apomorphine rotation test suggests that BZAD-01 may be a useful adjunct to levodopa monotherapy.

    Original languageEnglish
    Pages (from-to)85-90
    Number of pages6
    JournalBrain Research Bulletin
    Volume78
    Issue number2-3
    DOIs
    Publication statusPublished - 16 Feb 2009

    Keywords

    • 6-Hydroxydopamine
    • Apomorphine
    • Locomotion
    • NMDA receptor antagonist
    • Parkinsonism
    • Rotation

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    Warraich, S. T., Allbutt, H. N., Billing, R., Radford, J., Coster, M. J., Kassiou, M., & Henderson, J. M. (2009). Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model. Brain Research Bulletin, 78(2-3), 85-90. https://doi.org/10.1016/j.brainresbull.2008.08.023