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

Abstract

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.