Halogenated aromatic hydrocarbons suppress CA1 field excitatory postsynaptic potentials in rat hippocampal slices.
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Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biphenyls (PCBs) and dibenzo-p-dioxins (PCDDs), alter cognitive function and learning. The cellular basis of HAH-induced alteration of brain function is not well-understood. The hippocampus is a likely site of toxic action because of its well-known roles in learning and memory, as well as its propensity to accumulate environmental neurotoxicants. A hippocampal function that can be measured readily is evoked excitatory postsynaptic potentials (EPSPs), which are an index of excitatory synaptic function. In this study, effects of HAHs on EPSPs were characterized in hippocampal slices from adolescent to adult male Sprague-Dawley rats. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4-TCDD were used because these HAHs are prototypical potent and weak aryl hydrocarbon (Ah) receptor agonists, respectively. 2,2',5,5'-Tetrachlorobiphenyl (TCB) was used as a prototypical ortho-substituted PCB, which acts through Ah receptor-independent pathways. For each hippocampal slice, peak amplitudes of EPSPs during a 15-min recording period (1 recording/min) were averaged and used as baseline (100%). Subsequent EPSPs were expressed as percentage of baseline. TCDD and 1,2,3,4-TCDD did not alter EPSPs in slices from the middle third of the hippocampus. However, in ventral slices, TCDD significantly decreased EPSPs, whereas 1,2,3,4-TCDD was inactive. TCB decreased EPSPs in both middle and ventral slices at half-maximal stimulation. An unexpected reversal of inhibition was observed within 30 min of continuous application of TCDD or TCB. In ventral slices, L-type calcium channel blocker nifedipine blocked inhibition of EPSPs induced by TCDD but not EPSPs inhibited by TCB. These results suggest that, while TCB-induced inhibition of EPSPs occurs through an unknown mechanism, TCDD-induced inhibition of EPSPs was mediated by L-type calcium channel activity in a congener-specific manner.
author list (cited authors)
Hong, S. J., Grover, C. A., Safe, S. H., Tiffany-Castiglioni, E., & Frye, G. D.
complete list of authors
Hong, SJ||Grover, CA||Safe, SH||Tiffany-Castiglioni, E||Frye, GD