Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease

Figure 2

Schematic representation of the activity of the cortical-basal ganglia circuits in normal subjects (a) and in patients with Parkinson’s disease/Parkinsonism (b), resulting in a possible compensatory upregulation of receptors in various nuclei (STN, GPi, and SNr), which are overactive in PD. In PD, the underactivity of GABAergic neurons of the putamen and caudate projecting to GPi and SNr through the direct (D) pathway (b) may result in compensatory upregulation of receptors [39] in deafferented brain structures, namely, the GPi and SNr (b). Similarly, we can hypothesize that in PD the decreased GABAergic inhibition exerted by the external globus pallidus (GPe) through the indirect (I) pathway on the glutamatergic neurons of the STN and the GABAergic neurons of the GPi and SNr (b) may result in compensatory upregulation of receptors in such deafferented brain structures (STN, GPi, and SNr). Such compensatory upregulation of receptors in deafferented brain structures (STN, GPi, and SNr) could be more marked in PD patients who, after the administration of zolpidem, show more evident beneficial effects on Parkinsonian motor symptoms and show no or minimal drowsiness. White arrows = excitatory connections; black arrows = inhibitory connections.

(a) Normal

(b) Parkinson’s disease