2. Academic Validation
  3. Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA+parafascicular lesions

Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA+parafascicular lesions

  • Brain Res Bull. 2009 Feb 16;78(2-3):91-6. doi: 10.1016/j.brainresbull.2008.10.004.
L Truong 1,  H N Allbutt,  M J Coster,  M Kassiou,  J M Henderson
Affiliations

Affiliation

  • 1 Department of Pharmacology, Bosch Building, Bosch Institute & School of Medical Sciences, University of Sydney, NSW 2006, Australia.
PMID: 19007866 DOI: 10.1016/j.brainresbull.2008.10.004
Abstract

Experimental lesions involving the parafascicular (Pf) nucleus and medial forebrain bundle (MFB) may model to some extent the pathological loss of glutamatergic neurons from the centromedian-parafascicular (CM-Pf) complex and nigral dopaminergic cell loss observed clinically at post-mortem in Parkinson's disease (PD) cases. Our study investigated whether there were alterations in symptomatology in such rats with unilateral 6-OHDA+Pf lesions after treatment with either a selective NR1A/NR2B NMDA antagonist and/or l-dopa. Rats were given dual surgery to the MFB with 6-hydroxydopamine (6-OHDA) and Pf with N-methyl-d-aspartate (NMDA). (i) An NR1A/NR2B selective NMDA antagonist (BZAD-01; 10mg/kg), (ii) l-dopa (25mg/kg), (iii) BZAD-01+l-dopa (10mg/kg; 25mg/kg) or (iv) vehicle solution were administered for 6 weeks, during which behavioural testing was performed. BZAD-01 improved postural asymmetry in the first month as well as apomorphine-induced rotation. The latter was also improved by l-dopa in this model. These data support the use of selective NR1/NR2B NMDA antagonists in the therapeutics of PD.

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