Zolpidem modulates GABA(A) receptor function in subthalamic nucleus.
The subthalamic nucleus occupies a position in the indirect pathway of basal ganglia circuit, which plays an important role in the movement regulation. Zolpidem is an imidazopyridine agonist with a high affinity on the benzodiazepine site of GABA(A) receptors containing alpha 1 subunit. Recently, zolpidem has been reported to be useful in treating subgroups of parkinsonian patients. A high density of zolpidem binding sites has been shown in rat subthalamic nucleus. To further investigate the modulation of zolpidem on GABA(A) receptor-mediated inhibitory synaptic current in subthalamic nucleus, whole-cell patch clamp recordings were used in the present study. Zolpidem at 100nM significantly prolonged the decay time and rise time of miniature inhibitory postsynaptic currents, with no effect on the amplitude and frequency. The benzodiazepine antagonist flumazenil could completely block the potentiation induced by zolpidem, confirming the specificity on the benzodiazepine site. At a high concentration of 1 microM, zolpidem significantly increased the decay time, rise time, amplitude and frequency of miniature inhibitory postsynaptic currents. In the behaving rats, unilateral microinjection of zolpidem into subthalamic nucleus induced a significant contralateral rotation. The present findings on the effect of zolpidem in subthalamic nucleus provide a rationale for further investigations into its potential in the treatment of Parkinson's disease.
Chen
Lei
L
Department of Physiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China. chenleiqd@163.com
Xie
Jun-Xia
JX
Fung
Kam-Shuen
KS
Yung
Wing-Ho
WH
D000818:Animals; D005442:Flumazenil / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018755:GABA Agonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011725:Pyridines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem