Modulation of synaptic GABAA receptor function by zolpidem in substantia nigra pars reticulata.
OBJECTIVE
The substantia nigra pars reticulata (SNr) constitutes one of the output centers of the basal ganglia, and its abnormal activity is believed to contribute to some basal ganglia motor disorders. Different lines of evidence revealed a major contribution of GABAA receptor-mediated synaptic inhibition in controlling the activity of SNr. The benzodiazepine binding site within the GABAA receptor is a modulation site of significant clinical interest. A high density of benzodiazepine binding sites has been reported in the rat SNr. In the present study, we investigate the effects of activating benzodiazepine binding sites in the SNr.


METHODS
Whole-cell patch-clamp recordings and motor behavior were applied.


RESULTS
Superfusion of zolpidem, a benzodiazepine binding agonist, at 100 nmol/L significantly prolonged the decay time of GABAA receptor-mediated postsynaptic currents. The prolongation on decay time induced by zolpidem was sensitive to the benzodiazepine antagonist flumazenil, confirming the specificity on the benzodiazepine site. Zolpidem at 1 micromol/L exerted a stronger prolongation on the decay time. A further experiment was performed on behaving rats. A unilateral microinjection of zolpidem into the rat SNr caused a robust contralateral rotation, which was significantly different from that of control animals receiving the vehicle injection.


CONCLUSIONS
The present in vitro and in vivo findings that zolpidem significantly potentiated GABA currents and thus inhibited the activity of the SNr provide a rationale for further investigations into its potential in the treatment of basal ganglia disorders.
Zhang
Li-li
LL
Department of Physiology, Qingdao University, Qingdao 266071, China.
Chen
Lei
L
Xue
Yan
Y
Yung
Wing-ho
WH
D000818:Animals; D004298:Dopamine / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018755:GABA Agonists; D011725:Pyridines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem; D004298:Dopamine