Modulation of the activity of globus pallidus by dopamine D1-like receptors in parkinsonian rats

Abstract

Morphological studies have shown that the globus pallidus receives dopaminergic innervation from the collaterals of nigrostriatal fibers. Dopamine D1-like receptors are expressed at both pre- and postsynaptic membrane. In the present study, we investigate the in vivo electrophysiological and behavioral effects of pallidal dopamine D1-like receptors in parkinsonian rats. On the lesioned side of 6-hydroxydopamine (6-OHDA) parkinsonian rats, micropressure ejection of dopamine D1-like receptor agonist, SKF38393, increased (88.2 ± 18.6%) the firing rate in 10 out of the 32 pallidal neurons, but decreased (49.5 ± 6.1%) the firing rate in 14 out of the 32 neurons. Furthermore, on the unlesioned side of parkinsonian rats, SKF38393 increased (43.0 ± 6.3%) the firing rate in 9 out of the 30 pallidal neurons, but decreased (47.1 ± 4.8%) the firing rate in 13 out of the 30 neurons. In behaving rats, unilateral microinjection of SKF38393 led to contralateral deflection in the presence of systemic haloperidol administration. The selective dopamine D1-like receptor antagonist, SCH23390, blocked both SKF38393-induced electrophysiological and behavioral effects. Combining electrophysiological and behavioral findings, we concluded that activation of dopamine D1-like receptors modulates the activity of globus pallidus neurons in rats.