Selective putaminal excitotoxic lesions in non-human primates model the movement disorder of Huntington disease.
While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease.
Burns
L H
LH
Neuroregeneration Laboratory, McLean Hospital, Belmont, MA 02178, USA.
Pakzaban
P
P
Deacon
T W
TW
Brownell
A L
AL
Tatter
S B
SB
Jenkins
B G
BG
Isacson
O
O
D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum; D004195:Disease Models, Animal; D006816:Huntington Disease; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009069:Movement Disorders; D011699:Putamen; D017378:Quinolinic Acid / Q000494:pharmacology
D017378:Quinolinic Acid