HALOGENATED AROMATIC-HYDROCARBONS SUPPRESS CA1 FIELD EXCITATORY POSTSYNAPTIC POTENTIALS IN RAT HIPPOCAMPAL SLICES

Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biph enyls (PCBs) and dibenzo-p-dioxins (PCDDs), alter cognitive function a nd learning. The cellular basis of HAH-induced alteration of brain fun ction is not well-understood. The hippocampus is a likely site of toxi c action because of its well-known roles in learning and memory, as we ll as its propensity to accumulate environmental neurotoxicants. A hip pocampal function that can be measured readily is evoked excitatory po stsynaptic potentials (EPSPs), which are an index of excitatory synapt ic function. In this study, effects of HAHs on EPSPs were characterize d in hippocampal slices from adolescent to adult male Sprague-Dawley r ats. 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 hydrocar bon (Ah) receptor agonists, respectively. 2,2',5,5'-Tetrachlorobipheny l (TCB) was used as a prototypical ortho-substituted PCB, which acts t hrough Ah receptor-independent pathways. For each hippocampal slice, p eak 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 alt er 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 sli ces at half-maximal stimulation. An unexpected reversal of inhibition was observed within 30 min of continuous application of TCDD or TCB. I n ventral slices, L-type calcium channel blocker nifedipine blocked in hibition of EPSPs induced by TCDD but not EPSPs inhibited by TCB. Thes e results suggest that, while TCB-induced inhibition of EPSPs occurs t hrough an unknown mechanism, TCDD-induced inhibition of EPSPs was medi ated by L-type calcium channel activity in a congener specific manner. (C) 1998 Academic Press.