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Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
A parametric assessment of GABA antagonist effects on paired-pulse facilitation in the rat anterior cingulate cortex
Sergiy O Sylantyev1, Chia-Ming Lee, Bai-Chuang Shyu
1JCSMR, Australian National University, Canberra, ACT 2600, Australia.
Abstract:
Paired-pulse facilitation (PPF) is a form of short-term plasticity that can be used qualitatively to characterize the synaptic effects of neuroactive compounds. As we have shown previously, CNQX has a marked effect on PPF which can be measured quantitatively. The aim of the present study was to examine quantitatively possible differences in the effects of the post- and pre-synaptic GABA antagonists on PPF in vitro. Experiments were performed on slices taken from the coronal anterior cingulate cortex (ACC) of Sprague-Dawley rats. The stimuli consisted of a pair of biphasic pulses with an inter-pulse interval of 40ms. Evoked extracellular field potentials in layers 2/3 of the ACC were recorded. Quantitative assessment of PPF was achieved by calculating two parameters, the PPFmax (theoretical maximal PPF) and the Stmax (stimulus intensity that produces the PPFmax). Picrotoxin treatment produced increases in both the PPFmax and Stmax, by increasing the stimulus producing the half-maximal effect. In contrast, CGP-55845 treatment produced an increase in only the PPFmax, which was due to an alteration in the asymptotic values of the response amplitudes. Our findings show that the effect of different GABA receptor antagonists on short-term synaptic facilitation in the ACC may be assessed and specified quantitatively.

