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DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.
LOSA, S. M., J. E. BALDWIN, A. F. JOHNSTONE, AND T. J. SHAFER. DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
The present study expands characterization of pyrethroid effects on network activity by examining deltamethrin (DM) and esfenvalerate (ESF) effects on spontaneous firing in networks of cortical neurons.
Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of interconnected neurons are not well described. Recently, it was demonstrated that deltamethrin inhibited spontaneous activity and decreased the burst duration of rat hippocampal neurons in vitro. The present study expands characterization of pyrethroid effects on network activity by examining deltamethrin (DM) and esfenvalerate (ESF) effects on spontaneous firing in networks of cortical neurons. Primary cultures of rat cortex were prepared from postnatal day 1 pups, and cells were plated onto multiple electrode arrays at a density of 200,000 cells/array. After 9-21 days in vitro, spontaneous network activity consisting of individual spikes and groups of spikes (bursts) developed and reached a stable level, at which time experiments were conducted. To limit the responses measured to glutamatergic networks, gabaergic input was blocked by addition of 10 μM bicuculline and 20 μM SCH 50911. These drugs increased the mean network firing (# of spikes/min) and bursting (#bursts/min) rates, as well as burst duration. DM or ESF stock solutions were prepared in 1:1 DMSO:ethanol, and were added at final concentrations between 10 nM and 10 μM. Both compounds caused a concentration-dependent inhibition of mean network spike and burst rates; at 10 μM, inhibition of mean spike rate exceeded 90% for DM and 80% for ESF. Both compounds also decreased burst duration in a concentration-dependent manner. Inhibition of mean spike rate by ESF was less potent (~3 μM; N= 2-6) than DM (~700 nM; N=6). These data demonstrate that pyrethroids inhibit spontaneous glutamatergic network activity in cortical neurons in a fashion similar to hippocampal neurons.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
NEUROPHYSIOLOGICAL TOXICOLOGY BRANCH