Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA+parafascicular lesions.
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.
Truong
L
L
Department of Pharmacology, Bosch Building, Bosch Institute & School of Medical Sciences, University of Sydney, NSW 2006, Australia.
Allbutt
H N
HN
Coster
M J
MJ
Kassiou
M
M
Henderson
J M
JM
D000284:Administration, Oral; D018663:Adrenergic Agents / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000473:pathology; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000473:pathology; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012399:Rotation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016202:N-Methylaspartate; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine