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Zolpidem role in the regulation of the rat substantia nigra pars reticulata with the subthalamic nuclear GABA_A receptor function

Author: ZhangLiLi
Tutor: ChenLei;RongYongHao
School: Qingdao University
Course: Physiology
Keywords: benzodiazepines zolpidem GABA_A receptors IPSCs substantia nigra pars reticulata zolpidem GABA_A receptors mIPSCs subthalamic nucleus
CLC: Q42
Type: Master's thesis
Year: 2006
Downloads: 32
Quote: 0
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Abstract


Effects of Zolpidem on GABA_A Receptors Mediated IPSCs in Rat Substantia Nigra Pars ReticulataThe 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 including Parkinson’s diseases. Different lines of evidence point to a major contribution of GABA_A receptors' dissertation">GABA_A receptors mediated synaptic inhibition in controlling the activities of SNr neurons. A very high density of benzodiazepine binding sites containing a1 subunit has been reported in the rat SNr, indicating the modulation on GABAa channel kinetics. Some clinic reports pointed out that the specific agonist zolpidem' dissertation">zolpidem had antiparkinsonian effects in some types of Parkinson’s patients. To investigate the possible effects of activating benzodiazepine binding sites by zolpidem, whole-cell patch-clamp recordings were made from SNr neurons in midbrain slices of young rats. Superfusion of 100 nM zolpidem significantly prolonged the decay time of both mIPSCs and sIPSCs by 40.65%±4.41% (n=6, P<0.01) and 49.90% ± 5.35% (n=7, P<0.01), respectively, without any change on their amplitude and frequency. A higer concentration (1μM) of zolpidem prolonged the decay time more potently (mlPSCs: 87.84%±8.06%, n=6; sIPSCs: 65.59%±10.38%, n=9). Furthermore, 1μM zolpidem increased the amplitude of mlPSCs (18.35%±5.14%, p<0.05) significantly, which indicated that postsynaptic GABAa receptors in SNr were not saturated by quantal release of GABA. In the behaviour test, zolpidem microinjected into rat SNr unilaterally caused a robust contralateral rotation (32.71±2.89turns/30min, n=7, P<0.01), significantly higher than that of control animals received saline injection. The present findings that zolpidem significantly potentiated GABA currents in SNr provides a rationale for further investigations into its potential in the treatment of Parkinson’s disease and epilepsy.Postgraduate student: Li-Li Zhang (Physiology)

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