SELECTIVE PUTAMINAL EXCITOTOXIC LESIONS IN NONHUMAN-PRIMATES MODEL THE MOVEMENT DISORDER OF HUNTINGTON DISEASE

While dyskinetic movements have been reported in primates with unilate ral excitotoxic lesions following stimulation by dopaminergic agonists , the presence and intensity of the dyskinetic syndromes have Varied e xtensively with size and location of lesion. With the intent of produc ing a more reliable behavioral model of Huntington disease, anatomical ly-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific r egions 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 D-1 specific receptor ligand SCH 39166 as a marker for striat al output neurons. The quality, frequency and duration of dyskinetic m ovements 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 th e anterior putamen or the head of the caudate, produced marked dystoni a and dyskinesia after apomorphine administration. While combined unil ateral lesions of the caudate and posterior putamen produced dyskinesi a similar to selective posterior putaminal lesions, combined unilatera l lesions of the anterior and posterior putamen did not elicit dyskine sia. On the basis of these results, one monkey received a bilateral se lective 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 d yskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the mov ement disorder of Huntington disease.