Hyperexcitability of the hippocampal CA1 and the dentate gyrus in rats subchronically exposed to a substitute for chlorofluorocarbons, 1-bromopropane vapor

Abstract

To investigate the effects on the central nervous system of subchronic exposure to 1-bromopropane (1-BP), which is a substitute for chlorofluorocarbons, we measured the hippocampal excitability of 1-BP-treated rats electrophysiologically. Male Wistar rats were exposed to 1-BP for 6-h in a day in an exposure chamber (1,500 ppm) for 4 wk. After the 1-, 3- and 4-wk inhalation, field excitatory postsynaptic potentials (fEPSPs), population spikes (PSs), fEPSP/spike (E/S) curve, paired-pulse profiles of fEPSP slopes and PS amplitudes recorded from CA1 pyramidal neurons, and dentate granule cells of the hippocampal slice obtained from the rats were analyzed. In 1-BP treated rats, E/S potentiation and a lower subthreshold of PSs were observed in the dentate gyrus (DG) after the 3 and 4-wk inhalation. Paired-pulse inhibition was reduced at 5-50 ms in the CA1 and at 5-20 ms in the DG after all of the inhalation. These changes were not associated with paired-pulse inhibition of fEPSPs. In the DG, the paired-pulse inhibition at the short interpulse intervals in rats exposed to 1-BP was pronounced by an application of A type gamma aminobutyric acid (GABA) receptor agonist pentobarbital. Impaired paired-pulse inhibition of granule cells at the short interpulse intervals was recovered after the application of N-methyl-D-aspartate (NMDA) type glutamate receptor antagonist DL-2-amino-5-phosphonopentanoic acid. Convulsing rats observed after the 4-wk inhalation exhibited multiple PSs in the DG, and their second component was abolished by an application of this antagonist. Inhalation of 1-BP increased the neuronal excitability in the hippocampal CA1 and the DG. The hyperexcitability of the granule cells in the DG was at least due to an over-activation of NMDA receptors.