Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys.
High-frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo-functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control.
Karachi
Carine
C
INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France. carine.karachi@gmail.com
Grabli
David
D
Baup
Nicolas
N
Mounayar
Stéphanie
S
Tandé
Dominique
D
François
Chantal
C
Hirsch
Etienne C
EC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000009:adverse effects; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects; D018682:GABA Agents / Q000009:adverse effects; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections / Q000379:methods; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology*; D009118:Muscimol / Q000009:adverse effects; D011930:Reaction Time / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000503:physiopathology*
D018682:GABA Agents; D009118:Muscimol; D001640:Bicuculline