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• W2083404274 startingPage "1170" @default.
• W2083404274 abstract "The recently discovered GABA_B receptor-positive allosteric modulators enhanced the potency and efficacy of GABA_B receptor agonists in in vitro experiments. These GABA_B modulators also attenuated reward and anxiety in behavioral experiments without causing the untoward side effects associated with GABA_B receptor activation by agonist administration and hence exhibited potential therapeutic utility. However, the underlying molecular mechanisms enabling the GABA_B allosteric modulators to dissociate from the GABA_B agonistic side effects remain elusive. To address this question, we have examined the effects of a typical GABA_B modulator, 2,6-di-<i>tert</i>-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930), on GABA_B receptor-mediated modulations of both the excitatory and the delayed inhibitory components of hippocampal CA1 synaptic transmission. Using baclofen as an agonist and a multielectrode recording system, we recorded GABA_B receptor-mediated modulations of both the field excitatory postsynaptic potentials and the population spikes simultaneously, as well as the paired-pulse inhibition of the population spike. We found that CGP7930 selectively enhanced the baclofen-induced modulation of synaptic inhibition without having any significant effects on the synaptic excitation. Our experiments have therefore revealed a pathway-selective differential modulation of synaptic transmission by CGP7930. This finding provides a synaptic mechanism to support the hypothesis that GABA_B potentiators may be a better therapeutic alternative than GABA_B agonists for central nervous system disorders." @default.
• W2083404274 created "2016-06-24" @default.
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• W2083404274 date "2006-02-28" @default.
• W2083404274 modified "2023-09-30" @default.
• W2083404274 title "Differential Modulation by the GABA_BReceptor Allosteric Potentiator 2,6-Di-<i>tert</i>-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930) of Synaptic Transmission in the Rat Hippocampal CA1 Area" @default.
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• W2083404274 doi "https://doi.org/10.1124/jpet.105.099176" @default.
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