Alterations in N-methyl-D-aspartate receptor binding in dystonic hamster brains.
The genetically dystonic hamster is an animal model of idiopathic dystonia that displays sustained abnormal movements and postures either spontaneously or in response to mild environmental stimuli. Previous pharmacological studies have shown that competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists exert potent antidystonic activity in this model, indicating that abnormal NMDA receptor function may be involved in the pathophysiology of this movement disorder. Autoradiographic analysis of NMDA receptor density in 67 brain regions, using the ligand [3H] N-(1-[2-thienyl]cyclohexyl)3,4-piperidine, which binds to the phencyclidine (PCP) site in the ion channel of the NMDA receptor channel complex, revealed that NMDA receptor binding is not substantially altered in dystonic hamster brains compared to age-matched controls. Nevertheless, there was a tendency towards enhanced binding during a dystonic attack in several regions, including a 25% increase in the ventrolateral thalamic nucleus (P < 0.05), which may be associated with altered basal ganglia output. While the data do not indicate widespread abnormalities in the PCP site of the NMDA complex, they do not exclude the possibility of more pronounced changes at other regulatory binding sites of the NMDA complex or other types of glutamate receptors in dystonia.
Nobrega
J N
JN
Clarke Institute of Psychiatry, Toronto, Ont., Canada.
Richter
A
A
Jiwa
D
D
Raymond
R
R
Löscher
W
W
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry; D006224:Cricetinae; D004421:Dystonia / Q000235:genetics / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009154:Mutation / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014316:Tritium
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D018698:Glutamic Acid; D010622:Phencyclidine