Deficits induced by quinolinic acid lesion to the striatum in a position discrimination and reversal task are ameliorated by permanent and temporary lesion to the globus pallidus: a potential novel treatment in a rat model of Huntington's disease.
Symptoms in the early stages of Huntington's disease (HD) are assumed to reflect basal ganglia circuit dysfunction secondary to degeneration of striatal projections to the external segment of the globus pallidus (GPe). The hypothesis that GPe lesion would ameliorate HD symptoms by "normalizing" the circuit's functioning was tested in a rat model of this disease. The performance of rats sustaining quinolinic acid lesion to the striatum (a rat model of HD) in a position discrimination and reversal task was compared with the performance of rats sustaining in addition a bilateral excitotoxic lesion to the globus pallidus (GP) carried out simultaneously with the striatal lesion (Experiment 1) or 1 month after the striatal lesion (Experiment 2), as well as a unilateral temporary lesion of the GP (Experiment 3). The striatal lesion-induced deficit in the task was effectively reversed by a bilateral excitotoxic GP lesion carried out simultaneously or 1 month after the striatal lesion, as well as by a temporary unilateral GP inactivation. Given that a similar dysfunction of basal ganglia circuitry is thought to subserve the behavioral alterations seen in quinolinic acid lesioned rats and some of the symptoms in HD, these results raise the possibility that lesion or inactivation of the GPe may alleviate some of HD symptoms.
Joel
Daphna
D
Department of Psychology, Tel-Aviv University, Tel-Aviv, Israel. djoel@post.tau.ac.il
Ayalon
Liat
L
Tarrasch
Ricardo
R
Weiner
Ina
I
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D004193:Discrimination Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects* / Q000473:pathology; D006816:Huntington Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007267:Injections; D008297:Male; D009415:Nerve Net / Q000187:drug effects* / Q000473:pathology; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D017378:Quinolinic Acid