Electrophysiological and behavioral effects of zolpidem in rat globus pallidus

The globus pallidus is believed to play a critical role in the normal function of the basal ganglia, and abnormal activity of its neurons may underlie some basal ganglia motor symptoms. A high density of benzodiazepine binding sites on GABA_A receptors has been reported in the rat globus pallidus. The present study investigates the effect of activating the benzodiazepine site by the agonist zolpidem. In in vitro slices, 100 nM of zolpidem significantly prolonged the half decay time of both miniature and spontaneous inhibitory postsynaptic currents by 30.1 ± 3.0% (n = 12) and 17.8 ± 2.4% (n = 16), respectively, with no effect on their amplitudes and frequencies. In the behaving animal, when zolpidem was microinjected into the globus pallidus unilaterally, it caused a robust ipsilateral rotation (26.4 ± 2.4 turns/30 min, n = 8), significantly higher than that of control animals receiving vehicle injection (1.3 ± 1.6 turns/30 min, n = 6). This effect was in agreement with the in vitro effect of zolpidem in enhancing the action of GABA on postsynaptic GABA_A receptors. All the effects of zolpidem, in vitro or in vivo, were sensitive to the benzodiazepine antagonist flumazenil, confirming the specificity on the benzodiazepine site. This finding on the effect of zolpidem on motor behavior provides a rationale for further investigations into its potential in the treatment of motor disorders originating from the basal ganglia.