Intrapallidal administration of 6-hydroxydopamine mimics in large part the electrophysiological and behavioral consequences of major dopamine depletion in the rat

P.M. Abedi, C. Delaville, P. De Deurwaerdère, W. Benjelloun, A. Benazzouz
Neuroscience. 2013-04-01; 236: 289-297
DOI: 10.1016/j.neuroscience.2013.01.043

PubMed
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In addition to GABA and glutamate innervations, the globus pallidus (GP) receives
dopamine afferents from the pars compacta of the substantia nigra (SNc), and in
turn, sends inhibitory GABAergic efferents to the subthalamic nucleus (STN) and
the pars reticulata of the substantia nigra (SNr). Nevertheless, the role of
dopamine in the modulation of these pallido-subthalamic and pallido-nigral
projections is not known. The present study aimed to investigate the effects of
intrapallidal injection of 6-hydroxydopamine (6-OHDA) on the electrical activity
of STN and SNr neurons using in vivo extracellular single unit recordings in the
rat and on motor behaviors, using the “open field” actimeter and the stepping
test. We show that intrapallidal injection of 6-OHDA significantly decreased
locomotor activity and contralateral paw use. Electrophysiological recordings
show that 6-OHDA injection into GP significantly increased the number of bursty
cells in the STN without changing the firing rate, while in the SNr neuronal
firing rate decreased and the proportion of irregular cells increased. Our data
provide evidence that intrapallidal injection of 6-OHDA resulted in motor
deficits paralleled by changes in the firing activity of STN and SNr neurons,
which mimic in large part those obtained after major dopamine depletion in the
classical rat model of Parkinson’s disease. They support the assumption that in
addition to its action in the striatum, dopamine mediates its regulatory function
at various levels of the basal ganglia circuitry, including the GP.

 

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