Sensorimotor deficits in a unilateral intrastriatal 6-OHDA partial lesion model of Parkinson's disease in marmoset monkeys.
Animal studies investigating the efficacy of neurotrophic factors as treatments for Parkinson's disease (PD) ideally require partial dopamine (DA) lesion models. The intrastriatal 6-hydroxydopamine (6-OHDA) lesion model may be suitable for this purpose. Although this model has been well characterized in rodents, it has not previously been used in monkeys. The goal of the present study was to characterize the behavioral effects of unilateral injections of 6-OHDA in the basal ganglia of common marmoset monkeys (Callithrix jacchus). Cell counts from tyrosine hydroxylase immunochemistry 5 months postlesion revealed DA cell loss in the substantia nigra on the lesioned side to approximately 46% of relative to the unlesioned side. 6-OHDA lesioned monkeys showed a variety of behavioral deficits. Apomorphine induced rotation and simple sensorimotor measures (head position bias and PD disability rating score) were most affected by the lesion. The largest deficits were seen at 1 or 2 weeks postsurgery but had recovered by week 10. 6-OHDA lesioned monkeys took longer to complete a more complex sensorimotor staircase task. At 3.5 months postlesion, 6-OHDA monkeys also showed deficits on an object retrieval task designed to measure sensorimotor planning and skilled hand use. alpha-Methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, reinstated those deficits which had undergone recovery in the lesioned animals and also exacerbated the deficits on the staircase task. This model has potential in assessing treatments for PD aimed at curtailing disease progression such as continuous delivery of neurotrophic factors.
Eslamboli
Andisheh
A
Department of Experimental Psychology, Downing Street, Cambridge CB2 3EB, UK.
Baker
Harry F
HF
Ridley
Rosalind M
RM
Annett
Lucy E
LE
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002144:Callithrix; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D004185:Disability Evaluation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011187:Posture; D011597:Psychomotor Performance / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase